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  • 1.
    Badiali, Luca
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Olszewski, Pawel K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nylander, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Vergoni, Anna V
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract2012In: BMC gastroenterology, ISSN 1471-230X, Vol. 12, p. 134-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.

    METHODS: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.

    RESULTS: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

    CONCLUSIONS: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.

  • 2.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Giedratis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Self-reported sleep disturbance is associated with Alzheimer's disease risk in men2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 9, p. 1090-1097Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the association between self-reported sleep disturbances and dementia risk.

    METHODS: Self-reported sleep disturbances and established risk factors for dementia were measured in men at ages 50 (n = 1574) and 70 (n = 1029) years. Dementia incidence was determined by reviewing their patient history between ages 50 and 90 years. In addition, plasma levels of β-amyloid (Aβ) peptides 1-40 and 1-42 were measured at ages 70, 77, and 82 years.

    RESULTS: Cox regression demonstrated that men with self-reported sleep disturbances had a higher risk of developing dementia (+33%) and Alzheimer's disease (AD, +51%) than men without self-reported sleep disturbances (both P < .05). Binary logistic regression showed the increased risk for both dementia (+114%) and AD (+192%) were highest when sleep disturbance was reported at age 70 years (both P < .001). No group differences were found in Aβ levels.

    CONCLUSION: Improving sleep quality may help reduce the neurodegenerative risk in older men.

  • 3.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nilsson, Emil K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vågesjö, Evelina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Massena, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Pettersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christoffersson, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zetterberg, Henrik
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute sleep deprivation increases serum levels of neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) in healthy young men2014In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 37, no 1, p. 195-198Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES:

    To investigate whether total sleep deprivation (TSD) affects circulating concentrations of neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) in humans. These factors are usually found in the cytoplasm of neurons and glia cells. Increasing concentrations of these factors in blood may be therefore indicative for either neuronal damage, impaired blood brain barrier function, or both. In addition, amyloid β (Aβ) peptides 1-42 and 1-40 were measured in plasma to calculate their ratio. A reduced plasma ratio of Aβ peptides 1-42 to 1-40 is considered an indirect measure of increased deposition of Aβ 1-42 peptide in the brain.

    DESIGN:

    Subjects participated in two conditions (including either 8-h of nocturnal sleep [22:30-06:30] or TSD). Fasting blood samples were drawn before and after sleep interventions (19:30 and 07:30, respectively).

    SETTING:

    Sleep laboratory.

    PARTICIPANTS:

    15 healthy young men.

    RESULTS:

    TSD increased morning serum levels of NSE (P = 0.002) and S-100B (P = 0.02) by approximately 20%, compared with values obtained after a night of sleep. In contrast, the ratio of Aβ peptides 1-42 to 1-40 did not differ between the sleep interventions.

    CONCLUSIONS:

    Future studies in which both serum and cerebrospinal fluid are sampled after sleep loss should elucidate whether the increase in serum neuron-specific enolase and S100 calcium binding protein B is primarily caused by neuronal damage, impaired blood brain barrier function, or is just a consequence of increased gene expression in non-neuronal cells, such as leukocytes.

  • 4.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Television Watching and Effects on Food Intake: Distress vs Eustress2015In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 175, no 3, p. 468-468Article in journal (Refereed)
  • 5.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, Heike
    German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Jonas, Wenke
    German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Woting, Anni
    German Inst Human Nutr Potsdam Rehbrucke, Dept Gastrointestinal Microbiol, Arthur Scheunert Allee 114-116, D-14558 Nuthetal, Germany..
    Blaut, Michael
    German Inst Human Nutr Potsdam Rehbrucke, Dept Gastrointestinal Microbiol, Arthur Scheunert Allee 114-116, D-14558 Nuthetal, Germany..
    Schuermann, Annette
    German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals2016In: Molecular Metabolism, ISSN 2212-8778, Vol. 5, no 12, p. 1175-1186Article in journal (Refereed)
    Abstract [en]

    Objective: Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown. Methods: In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-weight men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02: 45-07: 00 h), and after two nights of normal sleep (NS; sleep opportunity 22: 30-07: 00 h). Fecal samples were collected within 24 h before, and after two in-lab nights, of either NS or PSD. In addition, participants underwent an oral glucose tolerance test following each sleep intervention. Results: Microbiota composition analysis (V4 16S rRNA gene sequencing) revealed that after two days of PSD vs. after two days of NS, individuals exhibited an increased Firmicutes: Bacteroidetes ratio, higher abundances of the families Coriobacteriaceae and Erysipelotrichaceae, and lower abundance of Tenericutes (all P < 0.05) - previously all associated with metabolic perturbations in animal or human models. However, no PSD vs. NS effect on beta diversity or on fecal short-chain fatty acid concentrations was found. Fasting and postprandial insulin sensitivity decreased after PSD vs. NS (all P < 0.05). Discussion: Our findings demonstrate that short-term sleep loss induces subtle effects on human microbiota. To what extent the observed changes to the microbial community contribute to metabolic consequences of sleep loss warrants further investigations in larger and more prolonged sleep studies, to also assess how sleep loss impacts the microbiota in individuals who already are metabolically compromised. (C) 2016 The Author(s). Published by Elsevier GmbH.

  • 6.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Increased prefrontal and parahippocampal activation with reduced dorsolateral prefrontal and insular cortex activation to food images in obesity: a meta-analysis of fMRI studies.2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, p. e60393-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Obesity is emerging as the most significant health concern of the twenty-first century. A wealth of neuroimaging data suggest that weight gain might be related to aberrant brain function, particularly in prefrontal cortical regions modulating mesolimbic addictive responses to food. Nevertheless, food addiction is currently a model hotly debated. Here, we conduct a meta-analysis of neuroimaging data, examining the most common functional differences between normal-weight and obese participants in response to food stimuli.

    DATA SOURCE: We conducted a search using several journal databases and adhered to the 'Preferred Reporting Items for Systematic Reviews and Meta-analyses' (PRISMA) method. To this aim, 10 studies were found with a total of 126 obese participants, 129 healthy controls, equaling 184 foci (146 increased, 38 decreased activation) using the Activation Likelihood Estimation (ALE) technique. Out of the 10 studies, 7 investigated neural responses to food versus non-food images.

    RESULTS: In response to food images, obese in comparison to healthy weight subjects had increased activation in the left dorsomedial prefrontal cortex, right parahippocampal gyrus, right precentral gyrus and right anterior cingulate cortex, and reduced activation in the left dorsolateral prefrontal cortex and left insular cortex.

    CONCLUSIONS: Prefrontal cortex areas linked to cognitive evaluation processes, such as evaluation of rewarding stimuli, as well as explicit memory regions, appear most consistently activated in response to images of food in those who are obese. Conversely, a reduced activation in brain regions associated with cognitive control and interoceptive awareness of sensations in the body might indicate a weakened control system, combined with hypo-sensitivity to satiety and discomfort signals after eating in those who are prone to overeat.

  • 7.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Intestinal Gene Expression Profiling and Fatty Acid Responses to a High-fat Diet2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The gastrointestinal tract (GIT) regulates nutrient uptake, secretes hormones and has a crucial gut flora and enteric nervous system. Of relevance for these functions are the G protein-coupled receptors (GPCRs) and the solute carriers (SLCs). The Adhesion GPCR subfamily is known to mediate neural development and immune system functioning, whereas SLCs transport e.g. amino acids, fatty acids (FAs) and drugs over membranes. We aimed to comprehensively characterize Adhesion GPCR and SLC gene expression along the rat GIT. Using qPCR we measured expression of 78 SLCs as well as all 30 Adhesion GPCRs in a twelve-segment GIT model. 21 of the Adhesion GPCRs had a widespread (≥5 segments) or ubiquitous (≥11 segments) expression. Restricted expression patterns were characteristic for most group VII members. Of the SLCs, we found the majority (56 %) of these transcripts to be expressed in all GIT segments. SLCs were predominantly found in the absorption-responsible gut regions. Both Adhesion GPCRs and SLCs were widely expressed in the rat GIT, suggesting important roles. The distribution of Adhesion GPCRs defines them as a potential pharmacological target.

    FAs constitute an important energy source and have been implicated in the worldwide obesity increase. FAs and their ratios – indices for activities of e.g. the desaturase enzymes SCD-1 (SCD-16, 16:1n-7/16:0), D6D (18:3n-6/18:2n-6) and D5D (20:4n-6/20:3n-6) – have been associated with e.g. overall mortality and BMI. We examined whether differences in FAs and their indices in five lipid fractions contributed to obesity susceptibility in rats fed a high fat diet (HFD), and the associations of desaturase indices between lipid fractions in animals on different diets. We found that on a HFD, obesity-prone (OP) rats had a higher SCD-16 index and a lower linoleic acid (LA) proportions in subcutaneous adipose tissue (SAT) than obesity-resistant rats. Desaturase indices were significantly correlated between many of the lipid fractions. The higher SCD-16 may indicate higher SCD-1 activity in SAT in OP rats, and combined with lower LA proportions may provide novel insights into HFD-induced obesity. The associations between desaturase indices show that plasma measurements can serve as proxies for some lipid fractions, but the correlations seem to be affected by diet and weight gain.

    List of papers
    1. Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract
    Open this publication in new window or tab >>Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract
    Show others...
    2012 (English)In: BMC gastroenterology, ISSN 1471-230X, Vol. 12, p. 134-Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.

    METHODS: Using RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.

    RESULTS: We found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.

    CONCLUSIONS: Overall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-190104 (URN)10.1186/1471-230X-12-134 (DOI)000312734600001 ()23009096 (PubMedID)
    Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2013-04-02Bibliographically approved
    2. Comprehensive analysis of localization of 78 solute carrier genes throughout the subsections of the rat gastrointestinal tract
    Open this publication in new window or tab >>Comprehensive analysis of localization of 78 solute carrier genes throughout the subsections of the rat gastrointestinal tract
    Show others...
    2011 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 411, no 4, p. 702-707Article in journal (Refereed) Published
    Abstract [en]

    Solute carriers (SLCs), the second largest super-family of membrane proteins in the human genome, transport amino acids, sugars, fatty acids, inorganic ions, essential metals and drugs over membranes. To date no study has provided a comprehensive analysis of SLC localization along the entire GI tract. The aim of the present study was to provide a comprehensive, segment-specific description of the localization of SLC genes along the rat Cl tract by employing bioinformatics and molecular biology methods. The Unigene database was screened for rat SLC entries in the intestinal tissue. Using qPCR we measured expression of the annotated genes in the Cl tract divided into the following segments: the esophagus, the corpus and the antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum. Our Unigene-derived gene pool was expanded with data from in-house tissue panels and a literature search. We found 44 out of 78 (56%) of gut SLC transcripts to be expressed in all Cl tract segments, whereas the majority of remaining SLCs were detected in more than five segments. SLCs are predominantly expressed in gut regions with absorptive functions although expression was also found in segments unrelated to absorption. The proximal jejunum had the highest number of differentially expressed SLCs. In conclusion, SLCs are a crucial molecular component of the Cl tract, with many of them expressed along the entire GI tract. This work presents the first overall road map of localization of transporter genes in the Cl tract.

    Keywords
    Solute carriers, GI tract, RT-qPCR, Anatomical localization, Twelve subsections
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-159051 (URN)10.1016/j.bbrc.2011.07.005 (DOI)000294317300009 ()
    Available from: 2011-09-22 Created: 2011-09-21 Last updated: 2017-12-08Bibliographically approved
    3. Adipose tissue stearoyl-CoA desaturase 1 index is increased and linoleic acid is decreased in obesity-prone rats fed a high-fat diet
    Open this publication in new window or tab >>Adipose tissue stearoyl-CoA desaturase 1 index is increased and linoleic acid is decreased in obesity-prone rats fed a high-fat diet
    Show others...
    2013 (English)In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 12, no 2Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND

    Fatty acid (FA) composition and desaturase indices are associated with obesity and related metabolic conditions. However, it is unclear to what extent desaturase activity in different lipid fractions contribute to obesity susceptibility. Our aim was to test whether desaturase activity and FA composition are linked to an obese phenotype in rats that are either obesity prone (OP) or resistant (OR) on a high-fat diet (HFD).

    METHODS

    Two groups of Sprague-Dawley rats were given ad libitum (AL-HFD) or calorically restricted (HFD-paired; pair fed to calories consumed by chow-fed rats) access to a HFD. The AL-HFD group was categorized into OP and OR sub-groups based on weight gain over 5 weeks. Five different lipid fractions were examined in OP and OR rats with regard to proportions of essential and very long-chain polyunsaturated FAs: linoleic acid (LA), alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the stearoyl-CoA desaturase 1 (SCD-1) product 16:1n-7. FA ratios were used to estimate activities of the delta-5-desaturase (20:4n-6/20:3n-6), delta-6-desaturase (18:3n-6/18:2n-6), stearoyl-CoA desaturase 1 (SCD-1; 16:1n-7/16:0, SCD-16 and 18:1n-9/18:0, SCD-18), de novo lipogenesis (16:0/18:2n-6) and FA elongation (18:0/16:0). Fasting insulin, glucose, adiponectin and leptin concentrations were measured in plasma.

    RESULTS

    After AL-HFD access, OP rats had a significantly higher SCD-16 index and 16:1n-7 proportion, but a significantly lower LA proportion, in subcutaneous adipose tissue (SAT) triacylglycerols, as well as significantly higher insulin and leptin concentrations, compared with OR rats. No differences were found between the two phenotypes in liver (phospholipids; triacylglycerols) or plasma (cholesterol esters; phospholipids) lipid fractions or for plasma glucose or adiponectin concentrations. For the desaturase indices of the HFD-paired rats, the only significant differences compared with the OP or OR rats were higher SCD-16 and SCD-18 indices in SAT triacylglycerols in OP compared with HFD-paired rats.

    CONCLUSION

    The higher SCD-16 may reflect higher SCD-1 activity in SAT, which in combination with lower LA proportions may reflect higher insulin resistance and changes in SAT independent of other lipid fractions. Whether a lower SCD-16 index protects against diet-induced obesity is an interesting possibility that warrants further investigation.

    Keywords
    Desaturase, Diet-induced obesity, Fatty acid composition, High-fat diet, Linoleic acid, Obesity prone, Obesity resistant, Subcutaneous adipose tissue, SCD-1, Stearoyl-CoA desaturase
    National Category
    Nutrition and Dietetics Physiology
    Research subject
    Nutrition; Nutrition; Medical Biochemistry
    Identifiers
    urn:nbn:se:uu:diva-196188 (URN)10.1186/1476-511X-12-2 (DOI)000315111200001 ()23298201 (PubMedID)
    Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2018-01-11Bibliographically approved
    4. Fatty acid desaturase indices in rats: Associations between plasma, liver and adipose tissue lipid fractions and the effects of a high-fat diet and diet-induced obesity
    Open this publication in new window or tab >>Fatty acid desaturase indices in rats: Associations between plasma, liver and adipose tissue lipid fractions and the effects of a high-fat diet and diet-induced obesity
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Alterations in fatty acid (FA) desaturase indices are linked to obesity-related disorders. As desaturases affect FA composition increased understanding of their regulation across lipid fractions with varying functions is essential. In this study we have examined desaturases and selected FAs to establish their degree of co-regulation in five different lipid fractions and under different dietary conditions, including diet-induced obesity (DIO).

    Methods: Sprague-Dawley rats were randomly grouped into three groups, one fed a chow diet ad libitum (control) and two fed a high-fat diet (HFD): one ad libitum (AL-HFD) and the other one calorically pair fed to the chow-fed group (HFD-paired). FA composition in subcutaneous adipose tissue triacylglycerols (SAT-TG), liver (phospholipids and triacylglycerols) and plasma (phospholipids and cholesterol esters) was assessed. Delta-5 desaturase (D5D), delta-6 desaturase (D6D) and stearoyl-CoA-desaturase 1 (SCD-16) indices were calculated from product-to-precursor FA ratios and proportions of long-chain FAs were measured.

    Results: Positive correlations were found for the desaturase indices between the five lipid fractions, especially for SCD-16 and almost exclusively between liver and plasma fractions. Only SCD-16 in SAT-TG of the AL-HFD group correlated with gain in body weight. Independent of weight gain, the HFD decreased all SCD-16 indices and most FA proportions, but D5D and D6D indices were fraction- and tissue-dependently increased.

    Conclusion: Desaturase indices are especially correlated for SCD-16 and between lipid and plasma lipid fractions, suggesting that SAT-TG desaturation is differentially regulated compared with the other studied lipid fractions. The correlations are however influenced by diet and weight gain, further suggesting such factors should be taken into account when using desaturase indices.

    Keywords
    diet-induced obesity, delta-5, delta-6, scd-1, fatty acid composition, high-fat diet, subcutaneous adipose tissue, scd-16
    National Category
    Nutrition and Dietetics
    Research subject
    Nutrition; Nutrition
    Identifiers
    urn:nbn:se:uu:diva-196190 (URN)
    Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2013-04-02
  • 8.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Alsiö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Västermark, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Adipose tissue stearoyl-CoA desaturase 1 index is increased and linoleic acid is decreased in obesity-prone rats fed a high-fat diet2013In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 12, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Fatty acid (FA) composition and desaturase indices are associated with obesity and related metabolic conditions. However, it is unclear to what extent desaturase activity in different lipid fractions contribute to obesity susceptibility. Our aim was to test whether desaturase activity and FA composition are linked to an obese phenotype in rats that are either obesity prone (OP) or resistant (OR) on a high-fat diet (HFD).

    METHODS

    Two groups of Sprague-Dawley rats were given ad libitum (AL-HFD) or calorically restricted (HFD-paired; pair fed to calories consumed by chow-fed rats) access to a HFD. The AL-HFD group was categorized into OP and OR sub-groups based on weight gain over 5 weeks. Five different lipid fractions were examined in OP and OR rats with regard to proportions of essential and very long-chain polyunsaturated FAs: linoleic acid (LA), alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the stearoyl-CoA desaturase 1 (SCD-1) product 16:1n-7. FA ratios were used to estimate activities of the delta-5-desaturase (20:4n-6/20:3n-6), delta-6-desaturase (18:3n-6/18:2n-6), stearoyl-CoA desaturase 1 (SCD-1; 16:1n-7/16:0, SCD-16 and 18:1n-9/18:0, SCD-18), de novo lipogenesis (16:0/18:2n-6) and FA elongation (18:0/16:0). Fasting insulin, glucose, adiponectin and leptin concentrations were measured in plasma.

    RESULTS

    After AL-HFD access, OP rats had a significantly higher SCD-16 index and 16:1n-7 proportion, but a significantly lower LA proportion, in subcutaneous adipose tissue (SAT) triacylglycerols, as well as significantly higher insulin and leptin concentrations, compared with OR rats. No differences were found between the two phenotypes in liver (phospholipids; triacylglycerols) or plasma (cholesterol esters; phospholipids) lipid fractions or for plasma glucose or adiponectin concentrations. For the desaturase indices of the HFD-paired rats, the only significant differences compared with the OP or OR rats were higher SCD-16 and SCD-18 indices in SAT triacylglycerols in OP compared with HFD-paired rats.

    CONCLUSION

    The higher SCD-16 may reflect higher SCD-1 activity in SAT, which in combination with lower LA proportions may reflect higher insulin resistance and changes in SAT independent of other lipid fractions. Whether a lower SCD-16 index protects against diet-induced obesity is an interesting possibility that warrants further investigation.

  • 9.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Comment on Laker et al. Exercise Prevents Maternal High-Fat Diet-Induced Hypermethylation of the Pgc-1a Gene and Age-Dependent Metabolic Dysfunction in the Offspring. Diabetes 2014; 63:1605-16112014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 5, p. E5-E5Article in journal (Other academic)
  • 10.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Human obesity: FTO, IRX3, or both?2014In: Molecular metabolism, ISSN 2212-8778, Vol. 3, no 5, p. 505-506Article in journal (Other academic)
  • 11.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sleep duration and energy intake: timing matters2014In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 100, no 5, p. 1402-1403Article in journal (Other academic)
  • 12.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brandell, Jon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ros, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Hogenkamp, Pleunie S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Increased Impulsivity in Response to Food Cues after Sleep Loss in Healthy Young Men2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 8, p. 1786-1791Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo investigate whether acute total sleep deprivation (TSD) leads to decreased cognitive control when food cues are presented during a task requiring active attention, by assessing the ability to cognitively inhibit prepotent responses. MethodsFourteen males participated in the study on two separate occasions in a randomized, crossover within-subject design: one night of TSD versus normal sleep (8.5 hours). Following each nighttime intervention, hunger ratings and morning fasting plasma glucose concentrations were assessed before performing a go/no-go task. ResultsFollowing TSD, participants made significantly more commission errors when they were presented no-go food words in the go/no-go task, as compared with their performance following sleep (+56%; P<0.05). In contrast, response time and omission errors to go non-food words did not differ between the conditions. Self-reported hunger after TSD was increased without changes in fasting plasma glucose. The increase in hunger did not correlate with the TSD-induced commission errors. ConclusionsOur results suggest that TSD impairs cognitive control also in response to food stimuli in healthy young men. Whether such loss of inhibition or impulsiveness is food cue-specific as seen in obesitythus providing a mechanism through which sleep disturbances may promote obesity developmentwarrants further investigation.

  • 13.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Huang, Wenyu
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Ramsey, Kathryn Moynihan
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Waldeck, Nathan
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Cheng, Lei
    Northwestern Univ, Weinberg Coll Arts & Sci, Evanston, IL 60208 USA.
    Marcheva, Biliana
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Omura, Chiaki
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Kobayashi, Yumiko
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Peek, Clara Bien
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Levine, Daniel C.
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Dhir, Ravindra
    Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
    Awatramani, Raj
    Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA;Northwestern Univ, Ctr Genet Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    Bradfield, Christopher A.
    Univ Wisconsin, McArdle Lab Canc Res, Med Sch, Madison, WI 53706 USA.
    Wang, Xiaozhong A.
    Northwestern Univ, Weinberg Coll Arts & Sci, Dept Mol Sci, Evanston, IL 60208 USA.
    Takahashi, Joseph S.
    UT Southwestern Med Ctr, Dept Neurosci, Dallas, TX 75390 USA;UT Southwestern Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA.
    Mokadem, Mohamad
    Univ Iowa, Div Gastroenterol & Hepatol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
    Ahima, Rexford S.
    Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21205 USA.
    Bass, Joseph
    Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
    Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron2019In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 29, no 5, p. 1078-1091.e5Article in journal (Refereed)
    Abstract [en]

    The alignment of fasting and feeding with the sleep/ wake cycle is coordinated by hypothalamic neurons, though the underlying molecular programs remain incompletely understood. Here, we demonstrate that the clock transcription pathway maximizes eating during wakefulness and glucose production during sleep through autonomous circadian regulation of NPY/AgRP neurons. Tandem profiling of whole-cell and ribosome-bound mRNAs in morning and evening under dynamic fasting and fed conditions identified temporal control of activity-dependent gene repertoires in AgRP neurons central to synaptogenesis, bioenergetics, and neurotransmitter and peptidergic signaling. Synaptic and circadian pathways were specific to whole-cell RNA analyses, while bioenergetic pathways were selectively enriched in the ribosome-bound transcriptome. Finally, we demonstrate that the AgRP clock mediates the transcriptional response to leptin. Our results reveal that time-of-day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and food acquisition with the sleep/wake state.

  • 14.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lampola, Lauri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Axelsson, Emil K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Liethof, Lisanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hassanzadeh, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Yeganeh, Adine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Faramkologi 3.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, no 1, p. 5-10Article in journal (Refereed)
    Abstract [en]

    The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral satiety signal. Against this background, in the present study 16 men participated in two separate sessions: one night of PSD (4.25 h sleep) versus one night of full sleep (8.5 h sleep). In the morning following each sleep condition, subjects' oral cavities were rinsed with a 1-molar sucrose solution for 45 s, preceded and followed by blood sampling for repeated determination of plasma glucose and serum insulin concentrations (-3, +3, +5, +7, +10 and +20 min). Our main result was that PSD, compared with full sleep, was associated with significantly higher peripheral insulin resistance, as indicated by a higher fasting homeostasis model assessment of insulin resistance index (+16%, P = 0.025). In contrast, no CPIR was observed in any of the two sleep conditions. Our findings indicate that a single night of PSD is already sufficient to impair fasting insulin sensitivity in healthy men. In contrast, brief oral cavity rinsing with sucrose solution did not change serum insulin concentrations, suggesting that a blunted CPIR is an unlikely mechanism through which acute sleep loss causes metabolic perturbations during morning hours in humans.

  • 15.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Osler, Megan E.
    Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden..
    Voisin, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Vogel, Heike
    German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, D-14558 Nuthetal, Germany.;Univ Gothenburg, Sahlgrenska Acad, Dept Physiol, Inst Neurosci & Physiol, S-41137 Gothenburg, Sweden..
    Dickson, Suzanne L.
    Univ Gothenburg, Sahlgrenska Acad, Dept Physiol, Inst Neurosci & Physiol, S-41137 Gothenburg, Sweden..
    Zierath, Juleen R.
    Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden..
    Schioth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men2015In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 100, no 9, p. E1255-E1261Article in journal (Refereed)
    Abstract [en]

    Context: Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. Objective: This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. Intervention: In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (8MAL1, CLOCK, CRYT, PERT). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. Main Outcome Measures: In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P =.026) and in two promoter-interacting enhancer regions of PERT (+15%; P =.036; +9%; P =.026). In skeletal muscle, TSD vs sleep decreased gene expression of BMALT (-18%; P =.033) and CRY1 (-22%; P =.047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 932 vs 3178 723 nmol/L; P =.039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 1.63 vs 6.59 1.32 mmol/L; P =.011). Conclusions: Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

  • 16.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Osorio, Ricardo S
    Center for Brain Health, NYU Langone Medical Center, New York.
    Varga, Andrew W
    NYU Sleep Disorders Center, NYU Langone Medical Center, New York.
    Kam, Korey
    NYU Sleep Disorders Center, NYU Langone Medical Center, New York.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease2017In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 31, p. 102-111Article, review/survey (Refereed)
    Abstract [en]

    During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood-brain barrier function - conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.

  • 17.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rångtell, Frida H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Axelsson, Emil K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Yeganeh, Adine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, Heike
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol & Endocrinol, Gothenburg, Sweden..
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Dickson, Suzanne L.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol & Endocrinol, Gothenburg, Sweden..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Short Sleep Makes Declarative Memories Vulnerable to Stress in Humans2015In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 38, no 12, p. 1861-1868Article in journal (Refereed)
    Abstract [en]

    Study Objective: This study sought to investigate the role of nocturnal sleep duration for the retrieval of oversleep consolidated memories, both prior to and after being cognitively stressed for similar to 30 minutes the next morning. Design: Participants learned object locations (declarative memory task comprising 15 card pairs) and a finger tapping sequence (procedural memory task comprising 5 digits) in the evening. After learning, participants either had a sleep opportunity of 8 hours (between similar to 23:00 and similar to 07:00, full sleep condition) or they could sleep between similar to 03:00 and similar to 07:00 (short sleep condition). Retrieval of both memory tasks was tested in the morning after each sleep condition, both before (similar to 08:30) and after being stressed (similar to 09:50). Setting: Sleep laboratory. Participants: 15 healthy young men. Results: The analyses demonstrated that oversleep memory changes did not differ between sleep conditions. However, in their short sleep condition, following stress hallmarked by increased subjective stress feelings, the men were unable to maintain their pre-stress performance on the declarative memory task, whereas their performance on the procedural memory task remained unchanged. While men felt comparably subjectively stressed by the stress intervention, overall no differences between pre- and post-stress recalls were observed following a full night of sleep. Conclusions: The findings suggest that 8-h sleep duration, within the range recommended by the US National Sleep Foundation, may not only help consolidate newly learned procedural and declarative memories, but also ensure full access to both during periods of subjective stress.

  • 18.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sand, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Liethof, Lisanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lampola, Lauri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hassanzadeh, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Axelsson, Emil K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Yeganeh, Adine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ros, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Learning and sleep-dependent consolidation of spatial and procedural memories are unaltered in young men under a fixed short sleep schedule2016In: Neurobiology of Learning and Memory, ISSN 1074-7427, E-ISSN 1095-9564, Vol. 131, p. 87-94Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate if a fixed short sleep schedule impairs one of the main functions of sleep, which is to consolidate newly learned memories. Methods: Sixteen young men participated in two experimental conditions, each of which lasted for 3 consecutive days and nights in our laboratory: a short sleep schedule (4.25-h sleep opportunity per night) versus a normal sleep schedule (8.5 h per night). In the evening after two experimental nights, participants learned locations of 15 card pairs (spatial memory task) and a procedural finger tapping sequence task. Post-sleep retrieval of both memory tasks was tested the next morning. Results: The short sleep schedule, compared with the normal sleep schedule, considerably altered sleep characteristics, e.g. the proportion of time in slow-wave sleep increased across the three experimental nights. In contrast, neither learning in the evening of day 2, nor subsequent overnight memory consolidation (i.e. concerning the change in memory performance between pre-sleep learning on day 2 and post sleep retrieval on day 3) differed between the normal and short sleep schedule conditions. Conclusions: Our findings suggest that learning in the evening and subsequent sleep-dependent consolidation of procedural and spatial memories are unaltered in young men living under a fixed short sleep schedule. Future studies are warranted to validate our findings in other groups (e.g. adolescents and older subjects) and after more prolonged chronic sleep loss paradigms.

  • 19.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Determinants of Shortened, Disrupted, and Mistimed Sleep and Associated Metabolic Health Consequences in Healthy Humans2015In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, no 4, p. 1073-1080Article in journal (Refereed)
    Abstract [en]

    Recent increases in the prevalence of obesity and type 2 diabetes mellitus (T2DM) in modern societies have been paralleled by reductions in the time their denizens spend asleep. Epidemiological studies have shown that disturbed sleepcomprising short, low-quality, and mistimed sleepincreases the risk of metabolic diseases, especially obesity and T2DM. Supporting a causal role of disturbed sleep, experimental animal and human studies have found that sleep loss can impair metabolic control and body weight regulation. Possible mechanisms for the observed changes comprise sleep loss-induced changes in appetite-signaling hormones (e.g., higher levels of the hunger-promoting hormone ghrelin) or hedonic brain responses, altered responses of peripheral tissues to metabolic signals, and changes in energy intake and expenditure. Even though the overall consensus is that sleep loss leads to metabolic perturbations promoting the development of obesity and T2DM, experimental evidence supporting the validity of this view has been inconsistent. This Perspective aims at discussing molecular to behavioral factors through which short, low-quality, and mistimed sleep may threaten metabolic public health. In this context, possible factors that may determine the extent to which poor sleep patterns increase the risk of metabolic pathologies within and across generations will be discussed (e.g., timing and genetics).

  • 20.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Efficacy of antibody-based therapies to treat Alzheimer's disease: Just a matter of timing?2014In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 57, p. 104-106Article in journal (Refereed)
    Abstract [en]

    A pharmaceutical intervention that has received great attention in recent years for treating Alzheimer's disease (AD) is the use of antibodies targeting amyloid beta (A beta) in the brain, as the formation of A beta plaques is considered as being the driving force for the development and progression of AD. Recently, a Phase III trial in patients with mild-to-moderate AD has provided ambivalent evidence for the efficacy of this intervention. In this trial, the intravenous administration of bapineuzumab, a monoclonal antibody targeting A beta in the brain, for 78 weeks led to a reduction of cerebrospinal fluid levels of phosphorylated tau and evidence for lower A beta accumulation in the brain of AD patients who carried APOE epsilon 4. However, this treatment did not improve clinical outcomes (e.g. the rate of cognitive decline) in these patients. Similar null results with respect to the rate of cognitive decline were found in a separate Phase III clinical trial after treatment with solanezumab. Based on these findings, one conclusion could be that antibodies targeting A beta in the brain may unfold their highest efficacy when given before the development of clinical AD symptoms, i.e. during a period where neurodegeneration but not cognitive loss represents the major pathology. Another conclusion could be that antibody-based pharmaceutical interventions may fail to slow the progress of cognitive loss in patients who have AD because of their solely pharmaceutical therapeutic approach. Leisure activities that require patients' mental and physical abilities (e.g. exercise) are associated with a reduced risk of developing dementia. In the same manner, they may help to curb the progress of this devastating disease. Thus, combining the use of antibodies targeting A beta with therapeutic strategies that require patients' mental and physical abilities might help tackle the neurodegenerative dynamics and cognitive loss both in patients with AD, and its prodromal state, mild cognitive impairment.  

  • 21.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schonke, Milena
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Westholm, Jakub Orzechowski
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden.
    Mi, Jia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Binzhou Med Univ, Med & Pharmarcy Res Ctr, Yantai, Peoples R China.
    Chibalin, Alexander
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Voisin, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Osler, Megan
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Vogel, Heike
    German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Potsdam, Germany.
    Hornaeus, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Dickson, Suzanne L.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Gothenburg, Sweden.
    Lind, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Univ Utah, Dept Pathol, Salt Lake City, UT 84132 USA;Binzhou Med Univ, Precis Med, Yantai, Peoples R China.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zierath, Juleen R.
    Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans2018In: Science Advances, E-ISSN 2375-2548, Vol. 4, no 8, article id eaar8590Article in journal (Refereed)
    Abstract [en]

    Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.

  • 22.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Westholm, Orzechowski J.
    Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden..
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute Sleep Leads To Tissue-Specific Epigenetic And Transcriptional Responses In Healthy Humans2018In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, p. A5-A5Article in journal (Other academic)
  • 23.
    Chapman, Colin D.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Emil K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Victor C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rångtell, Frida H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, Heike
    Dickson, Suzanne L.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Hogenkamp, Pleunie S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute sleep deprivation increases food purchasing in men2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 12, p. E555-E560Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate if acute sleep deprivation affects food purchasing choices in a mock supermarket.

    Design and Methods

    On the morning after one night of total sleep deprivation (TSD) or after one night of sleep, 14 normal-weight men were given a fixed budget (300 SEKapproximately 50 USD). They were instructed to purchase as much as they could out of a possible 40 items, including 20 high-caloric foods (>2 kcal/g) and 20 low-caloric foods (<2 kcal/g). The prices of the high-caloric foods were then varied (75%, 100% (reference price), and 125%) to determine if TSD affects the flexibility of food purchasing. Before the task, participants received a standardized breakfast, thereby minimizing the potential confound produced by hunger. In addition, morning plasma concentrations of the orexigenic hormone ghrelin were measured under fasting conditions.

    Results

    Independent of both type of food offered and price condition, sleep-deprived men purchased significantly more calories (+9%) and grams (+18%) of food than they did after one night of sleep (both P<0.05). Morning plasma ghrelin concentrations were also higher after TSD (P<0.05). However, this increase did not correlate with the effects of TSD on food purchasing.

    Conclusions

    This experiment demonstrates that acute sleep loss alters food purchasing behavior in men.

  • 24.
    Chapman, Colin D.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Victor C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Thune, Hanna A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Le Greves, Madeleine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Watching TV and Food Intake: The Role of Content2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e100602-Article in journal (Refereed)
    Abstract [en]

    Obesity is a serious and growing health concern worldwide. Watching television (TV) represents a condition during which many habitually eat, irrespective of hunger level. However, as of yet, little is known about how the content of television programs being watched differentially impacts concurrent eating behavior. In this study, eighteen normal-weight female students participated in three counter-balanced experimental conditions, including a 'Boring' TV condition (art lecture), an 'Engaging' TV condition (Swedish TV comedy series), and a no TV control condition during which participants read (a text on insects living in Sweden). Throughout each condition participants had access to both high-calorie (M&Ms) and low-calorie (grapes) snacks. We found that, relative to the Engaging TV condition, Boring TV encouraged excessive eating (+52% g, P = 0.009). Additionally, the Engaging TV condition actually resulted in significantly less concurrent intake relative to the control 'Text' condition (235% g, P = 0.05). This intake was driven almost entirely by the healthy snack, grapes; however, this interaction did not reach significance (P = 0.07). Finally, there was a significant correlation between how bored participants were across all conditions, and their concurrent food intake (beta = 0.317, P = 0.02). Intake as measured by kcals was similarly patterned but did not reach significance. These results suggest that, for women, different TV programs elicit different levels of concurrent food intake, and that the degree to which a program is engaging (or alternately, boring) is related to that intake. Additionally, they suggest that emotional content (e. g. boring vs. engaging) may be more associated than modality (e. g. TV vs. text) with concurrent intake.

  • 25.
    Gremel, Gabriela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Fagerberg, Linn
    Hallström, Björn
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sjöstedt, Evelina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling.2015In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 50, no 1, p. 46-57Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The gastrointestinal tract (GIT) is subdivided into different anatomical organs with many shared functions and characteristics, but also distinct differences. We have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to describe the gene and protein expression patterns that define the human GIT.

    METHODS: RNA sequencing data derived from stomach, duodenum, jejunum/ileum and colon specimens were compared to gene expression levels in 23 other normal human tissues analysed with the same method. Protein profiling based on immunohistochemistry and tissue microarrays was used to sub-localize the corresponding proteins with GIT-specific expression into sub-cellular compartments and cell types.

    RESULTS: Approximately 75 % of all human protein-coding genes were expressed in at least one of the GIT tissues. Only 51 genes showed enriched expression in either one of the GIT tissues and an additional 83 genes were enriched in two or more GIT tissues. The list of GIT-enriched genes with validated protein expression patterns included various well-known but also previously uncharacterised or poorly studied genes. For instance, the colon-enriched expression of NXPE family member 1 (NXPE1) was established, while NLR family, pyrin domain-containing 6 (NLRP6) expression was primarily found in the human small intestine.

    CONCLUSIONS: We have applied a genome-wide analysis based on transcriptomics and antibody-based protein profiling to identify genes that are expressed in a specific manner within the human GIT. These genes and proteins constitute important starting points for an improved understanding of the normal function and the different states of disease associated with the GIT.

  • 26.
    Hogenkamp, Pleunie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chapman, Colin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, Heike
    Department of Physiology/Endocrinology, The Sahlgrenska Academy at the University of Gothenburg.
    Hjorth, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zarei, Sanaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lundberg, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dickson, Suzanne
    Department of Physiology/Endocrinology, The Sahlgrenska Academy at the University of Gothenburg.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Calorie anticipation alters food intake after low-caloric but not high-caloric preloads2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 8, p. 1548-1553Article in journal (Refereed)
    Abstract [en]

    Objective: Cognitive factors and anticipation are known to influence food intake. The current study examined the effect of anticipation and actual consumption of food on hormone (ghrelin, cortisol, insulin) and glucose levels, appetite and ad libitum intake, to assess whether changes in hormone levels might explain the predicted differences in subsequent food intake.

    Design and Methods: During four breakfast sessions, participants consumed a yogurt preload that was either low-caloric (LC; 180 kcal/300 g) or high-caloric (HC; 530 kcal/300 g), and were provided with either consistent or inconsistent calorie information (i.e. stating the caloric content of the preload was low or high). Appetite ratings and hormone and glucose levels were measured at baseline (t=0), after providing the calorie information about the preload (t=20), after consumption of the preload (t=40) and just before ad libitum intake (t=60).

    Results: Ad libitum intake was lower after HC preloads (as compared to LC preloads; p<0.01). Intake after LC preloads was higher when provided with (consistent) LC-information (467±254 kcal) as compared to (inconsistent) HC-information (346±210 kcal), but intake after the HC preloads did not depend on the information provided (LC-info: 290±178 kcal, HC-info: 333±179 kcal; caloric load*information p=0.03). Hormone levels did not respond in an anticipatory manner, and the post-prandial responses depended on actual calories consumed.

    Conclusions: These results suggest that both cognitive and physiological information determine food intake. When actual caloric intake was sufficient to produce physiological satiety, cognitive factors played no role; however, when physiological satiety was limited, cognitively-induced satiety reduced intake to comparable levels.

  • 27.
    Hogenkamp, Pleunie S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chapman, C D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, H
    Dickson, S L
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sweet taste perception not altered after acute sleep deprivation in healthy young men2013In: Somnologie, ISSN 1432-9123, E-ISSN 1439-054X, Vol. 17, no 2, p. 111-114Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We hypothesized that acutely sleep-deprived participants would rate ascending concentrations of sucrose as more intense and pleasant, than they would do after one night of normal sleep. Such a finding would offer a potential mechanism through which acute sleep loss could promote overeating in humans.

    METHOD:

    A total of 16 healthy normal-weight men participated in 2 conditions: sleep (permitted between 22:30 and 06:30 h) and total sleep deprivation (TSD) respectively. On the morning after regular sleep and TSD, circulating concentrations of ghrelin and glucose were measured. In addition, participants hunger level was assessed by means of visual analogue scales, both before and after a caloric preload. Finally, following the preload, participants rated both intensity and pleasantness of six orally presented yogurt probes with varying sucrose concentrations (2-29 %).

    RESULTS:

    Feelings of hunger were significantly more intense under both fasted and sated conditions when subjects were sleep-deprived. In contrast, the change in hunger induced by the preload was similar between the sleep and TSD conditions. Plasma concentrations of ghrelin were significantly higher under conditions of TSD, whereas plasma glucose did not differ between the conditions. No effects were found either on sweet taste intensity or on pleasantness after TSD.

    CONCLUSION:

    One night of TSD increases morning plasma concentrations of the hunger-promoting hormone ghrelin in healthy young men. In contrast, sweet taste perception was not affected by nocturnal wakefulness. This suggests that an altered sweet taste perception is an unlikely mechanism by which TSD enhances food intake.

  • 28.
    Hogenkamp, Pleunie S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Victor C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chapman, Colin D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, Heike
    Lundberg, Lina S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zarei, Sanaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rångtell, Frida H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Dickson, Suzanne L
    Brunström, Jeffrey M
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute sleep deprivation increases portion size and affects food choice in young men2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 9, p. 1668-1674Article in journal (Refereed)
    Abstract [en]

    Acute sleep loss increases food intake in adults. However, little is known about the influence of acute sleep loss on portion size choice, and whether this depends on both hunger state and the type of food (snack or meal item) offered to an individual. The aim of the current study was to compare portion size choice after a night of sleep and a period of nocturnal wakefulness (a condition experienced by night-shift workers, e.g. physicians and nurses). Sixteen men (age: 23 ± 0.9 years, BMI: 23.6 ± 0.6 kg/m2) participated in a randomized within-subject design with two conditions, 8-h of sleep and total sleep deprivation (TSD). In the morning following sleep interventions, portion size, comprising meal and snack items, was measured using a computer-based task, in both fasted and sated state. In addition, hunger as well as plasma levels of ghrelin were measured. In the morning after TSD, subjects had increased plasma ghrelin levels (13%, p = 0.04), and chose larger portions (14%, p = 0.02), irrespective of the type of food, as compared to the sleep condition. Self-reported hunger was also enhanced (p < 0.01). Following breakfast, sleep-deprived subjects chose larger portions of snacks (16%, p = 0.02), whereas the selection of meal items did not differ between the sleep interventions (6%, p = 0.13). Our results suggest that overeating in the morning after sleep loss is driven by both homeostatic and hedonic factors. Further, they show that portion size choice after sleep loss depend on both an individual's hunger status, and the type of food offered.

  • 29.
    Rosqvist, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Johansson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Arner, Peter
    Dahlman, Ingrid
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 7, p. 2356-2368Article in journal (Refereed)
    Abstract [en]

    Excess ectopic fat storage is linked to type 2 diabetes. The importance of dietary fat composition for ectopic fat storage in humans is unknown. We investigated liver fat accumulation and body composition during overfeeding saturated (SFA) or polyunsaturated (PUFA) fat. LIPOGAIN was a double-blind, parallel-group, randomized trial. Thirty-nine young and normal-weight individuals were overfed muffins high in SFA (palm oil) or n-6 PUFA (sunflower oil) for 7 weeks. Liver fat, visceral (VAT), subcutaneous abdominal (SAT), and total adipose tissue (TAT), pancreatic fat, and lean tissue was assessed by MRI. Transcriptomics were performed in SAT. Both groups gained similar weight. SFA however markedly increased liver fat compared with PUFA and caused 2-fold larger increase in VAT than PUFA. Conversely, PUFA caused a nearly 3-fold larger increase in lean tissue than SFA. Increase in liver fat directly correlated with changes in plasma SFA and inversely with PUFA. Genes involved in regulating energy dissipation, insulin resistance, body composition and fat cell differentiation in SAT were differentially regulated between diets, and associated with increased PUFA in SAT. In conclusion, overeating SFA promotes hepatic and visceral fat storage whereas excess energy from PUFA may instead promote lean tissue in healthy humans.

  • 30.
    Rångtell, Frida H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Karamchedu, Swathy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Andersson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Women and men are differentially affected by sleep loss with respect to cognitive performance and hunger regulation2017In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, p. A97-A97Article in journal (Other academic)
  • 31.
    Rångtell, Frida H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Karamchedu, Swathy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Andersson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Liethof, Lisanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Bucaro, Marcela Olaya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lampola, Lauri
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A single night of sleep loss impairs objective but not subjective working memory performance in a sex-dependent manner2019In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, no 1, article id e12651Article in journal (Refereed)
    Abstract [en]

    Acute sleep deprivation can lead to judgement errors and thereby increases the risk of accidents, possibly due to an impaired working memory. However, whether the adverse effects of acute sleep loss on working memory are modulated by auditory distraction in women and men are not known. Additionally, it is unknown whether sleep loss alters the way in which men and women perceive their working memory performance. Thus, 24 young adults (12 women using oral contraceptives at the time of investigation) participated in two experimental conditions: nocturnal sleep (scheduled between 22:30 and 06:30 hours) versus one night of total sleep loss. Participants were administered a digital working memory test in which eight-digit sequences were learned and retrieved in the morning after each condition. Learning of digital sequences was accompanied by either silence or auditory distraction (equal distribution among trials). After sequence retrieval, each trial ended with a question regarding how certain participants were of the correctness of their response, as a self-estimate of working memory performance. We found that sleep loss impaired objective but not self-estimated working memory performance in women. In contrast, both measures remained unaffected by sleep loss in men. Auditory distraction impaired working memory performance, without modulation by sleep loss or sex. Being unaware of cognitive limitations when sleep-deprived, as seen in our study, could lead to undesirable consequences in, for example, an occupational context. Our findings suggest that sleep-deprived young women are at particular risk for overestimating their working memory performance.

  • 32.
    Rångtell, Frida H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Karamchedu, Swathy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Andersson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    van Egmond, Lieve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hultgren, Tyra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Learning performance is linked to procedural memory consolidation across both sleep and wakefulness2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10234Article in journal (Refereed)
    Abstract [en]

    We investigated whether learning performance in a procedural finger tapping task before nocturnal sleep would predict performance gains after sleep in 60 young adults. Gains were defined as change in correctly tapped digit sequences between learning (12 trials administered in the evening) and retesting (3 trials administered in the morning after sleep). The same task was also administered to a separate wake group (N = 54 young adults), which learned in the morning and was retested in the evening. Learning performance was determined by either using the average performance on the last three learning trials or the average performance on the best three learning trials. Our results demonstrated an inverse association between learning performance and gains in procedural skill, i.e., good learners exhibited smaller performance gains across both wakefulness and sleep than poor learners. Regardless of learning performance, gains in finger tapping skills were greater after sleep than daytime wakefulness. Importantly, some of our findings were influenced by how learning performance was estimated. Collectively, these results suggest that learning performance and the method through which it is estimated may influence performance gains in finger tapping skills across both sleep and wakefulness.

  • 33.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Forsberg, Lars A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Self-reported sleep disturbances and prostate cancer morbidity and mortality in Swedish men: A longitudinal study over 40 years2018In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 27, no 6, article id e12708Article in journal (Refereed)
    Abstract [en]

    The present study, with an observational period of about 40 years, examined the association between self-reported sleep disturbances (i.e. problems with falling and staying asleep; use of hypnotics) and prostate cancer morbidity and mortality in initially 2322 men (all 50 years old at baseline). Self-reported sleep disturbances and established risk factors (e.g. age, lower urinary tract symptoms, smoking and family history of cancer) were measured at ages 50 and 70 years. Information about prostate cancer diagnosis and deaths as a result of prostate cancer was available from the National Cancer Registry and the Swedish Civil Registry of Morbidity. During the observational period, 263 participants developed prostate cancer (11% of the total cohort); 146 of them died as a result of prostate cancer. There was no association between sleep disturbances and prostate cancer morbidity or mortality (hazard ratio 1.09, 95% confidence interval (CI) 0.79, 1.52, and hazard ratio 1.21, 95% CI 0.77, 1.91, respectively). Similar findings were observed when examining associations between single sleep disturbance parameters and prostate cancer morbidity and mortality. Our study does not provide evidence that reports of sleep disturbances increase the risk of prostate cancer morbidity or mortality in middle to older-aged men. Therefore, assessing subjective sleep problems may not meaningfully help to identify men at risk of developing prostate cancer or dying of this devastating condition.

  • 34.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lack of association between self-reported insomnia symptoms and clamp-derived insulin sensitivity in elderly men2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 102, p. 256-260Article in journal (Refereed)
    Abstract [en]

    Insomnia-related sleep disruptions, such as short and disturbed sleep, have been tied to systemic insulin resistance in young adult populations. We therefore sought to confirm these findings in a cohort of elderly men. To this aim, we utilized variables from 980 men who participated in the investigation at age 70 of the Uppsala Longitudinal Study of Adult Men. Self-reported insomnia symptoms were assessed by questions about difficulty initiating sleep, early final awakening, and regular use of hypnotics. All participants also underwent the gold standard hyperinsulinemic-euglycemic clamp technique to assess the insulin sensitivity index (M/I). Finally, fasting blood was collected to measure free fatty acids (FFAs) and adiponectin. Differences in blood parameters between men with and those without insomnia were determined by ANCOVA, and were adjusted for lifestyle and cardio-metabolic risk factors. Our analysis yielded no differences in M/I, FFAs, and adiponectin between men with and those without insomnia symptoms. Analyses in non-diabetic and diabetic subsamples confirmed these negative findings. Our cross-sectional results therefore suggest that insomnia symptoms may have a minimal effect, if any, on measures of insulin sensitivity in elderly men. Given the observational design of our study, future studies are needed to determine whether experimental sleep manipulations influence systemic insulin sensitivity in elderly humans, as has previously been shown in young adult populations.

  • 35.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chapman, Colin D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Association between long sleep duration and increased risk of obesity and type 2 diabetes: A review of possible mechanisms2018In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 40, p. 127-134Article, review/survey (Refereed)
    Abstract [en]

    For the last two decades research has revealed an alarming association between short sleep duration and metabolic disorders. In tandem, the hormonal, behavioral, and genetic mechanisms underlying this relationship have been extensively investigated and reviewed. However, emerging evidence is revealing that excessive sleep duration has remarkably similar deleterious effects. Unfortunately, to date there has been little attention to what drives this connection. This narrative review therefore aims to summarize existing epidemiological findings, experimental work, and most importantly putative molecular and behavioral mechanisms connecting excessive sleep duration with both obesity and type 2 diabetes mellitus. It will also address recent findings suggesting a worrisome bidirectional effect such that metabolic disorders create a positive feedback loop which further perpetuates excessive sleep.

  • 36.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    van Egmond, Lieve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chapman, Colin D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Aiding sleep in type 2 diabetes: therapeutic considerations2018In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 6, no 1, p. 60-68Article, review/survey (Refereed)
    Abstract [en]

    Insomnia and obstructive sleep apnoea (OSA) are more prevalent in patients with type 2 diabetes than in the general population. Both insomnia and OSA have been linked to cardiometabolic alterations (eg, hypertension, increased activity of the sympathetic nervous system, and systemic insulin resistance) that can exacerbate the pathophysiology of type 2 diabetes. Improvement of sleep in patients with diabetes could therefore aid the treatment of diabetes. To help health practitioners choose the best clinical tool to improve their patients' sleep without detrimentally affecting glucose regulation, this Review critically analyses the effects of common treatments for insomnia and OSA on both sleep and glucose metabolism in patients with type 2 diabetes. These treatments include pharmaceutical sleep aids (eg, benzodiazepine receptor agonists, melatonin) and cognitive behavioural therapy for insomnia, continuous positive airway pressure for OSA, and lifestyle interventions.

1 - 36 of 36
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