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  • 1.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Div Prevent Med, Brigham & Womens Hosp, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Ahluwalia, Tarunveer S.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark.
    Editorial: The Role of Genetic and Lifestyle Factors in Metabolic Diseases2019In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 10, article id 475Article in journal (Other academic)
  • 2.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Prevent Med Div, Brigham & Womens Hosp, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Fatima, Syeda Sadia
    Aga Khan Univ, Dept Biol & Biomed Sci, Karachi, Pakistan.
    Rukh, Gull
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Smith, Caren E.
    Tufts Univ, Res Ctr Aging, Jean Mayer US Dept Agr, Nutr & Genom Lab, Boston, MA 02111 USA.
    Gene Lifestyle Interactions With Relation to Obesity, Cardiometabolic, and Cardiovascular Traits Among South Asians2019In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 10, article id 221Article, review/survey (Refereed)
    Abstract [en]

    The rapid rise of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) during the last few decades among South Asians has been largely attributed to a major shift in lifestyles including physical inactivity, unhealthy dietary patterns, and an overall pattern of sedentary lifestyle. Genetic predisposition to these cardiometabolic risk factors may have interacted with these obesogenic environments in determining the higher cardiometabolic disease prevalence. Based on the premise that gene-environment interactions cause obesity and cardiometabolic diseases, we systematically searched the literature and considered the knowledge gaps that future studies might ful fill. We identified only seven published studies that focused specifically on gene-environment interactions for cardiometabolic traits in South Asians, most of which were limited by relatively small sample and lack of replication. Some studies reported that the differences in metabolic response to higher physical activity and low caloric diet might be modified by genetic risk related to these cardiometabolic traits. Although studies on gene lifestyle interactions in cardiometabolic traits report significant interactions, future studies must focus on more precise assessment of lifestyle factors, investigation of a larger set of genetic variants and the application of powerful statistical methods to facilitate translatable approaches. Future studies should also be integrated with findings both using mechanistic studies through laboratory settings and randomized clinical trials for clinical outcomes.

  • 3. Elks, Cathy E
    et al.
    den Hoed, Marcel
    Zhao, Jing Hua
    Sharp, Stephen J
    Wareham, Nicholas J
    Loos, Ruth J F
    Ong, Ken K
    Variability in the heritability of body mass index: a systematic review and meta-regression.2012In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 3Article in journal (Refereed)
    Abstract [en]

    Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.

  • 4.
    Höglund, Erik
    et al.
    Norwegian Inst Water Res, Oslo, Norway;Univ Agder, Ctr Coastal Res, Kristiansand, Norway.
    Överli, Öyvind
    Norwegian Univ Life Sci, Fac Vet Med, Dept Food Safety & Infect Biol, Oslo, Norway.
    Winberg, Svante
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review2019In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 10, article id 158Article, review/survey (Refereed)
    Abstract [en]

    The essential amino acid L-tryptophan (Trp) is the precursor of the monoaminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Numerous studies have shown that elevated dietary Trp has a suppressive effect on aggressive behavior and post-stress plasma cortisol concentrations in vertebrates, including teleosts. These effects are believed to be mediated by the brain serotonergic system, even though all mechanisms involved are not well understood. The rate of 5-HT biosynthesis is limited by Trp availability, but only in neurons of the hindbrain raphe area predominantly expressing the isoform TPH2 of the enzyme tryptophan hydroxylase (TPH). In the periphery as well as in brain areas expressing TPH1, 5-HT synthesis is probably not restricted by Trp availability. Moreover, there are factors affecting Trp influx to the brain. Among those are acute stress, which, in contrast to long-term stress, may result in an increase in brain Trp availability. The mechanisms behind this stress induced increase in brain Trp concentration are not fully understood but sympathetic activation is likely to play an important role. Studies in mammals show that only a minor fraction of Trp is utilized for 5-HT synthesis whereas a larger fraction of the Trp pool enters the kynurenic pathway. The first stage of this pathway is catalyzed by the hepatic enzyme tryptophan 2,3-dioxygenase (TDO) and the extrahepatic enzyme indoleamine 2,3-dioxygenase (IDO), enzymes that are induced by glucocorticoids and pro-inflammatory cytokines, respectively. Thus, chronic stress and infections can shunt available Trp toward the kynurenic pathway and thereby lower 5-HT synthesis. In accordance with this, dietary fatty acids affecting the pro-inflammatory cytokines has been suggested to affect metabolic fate of Trp. While TDO seems to be conserved by evolution in the vertebrate linage, earlier studies suggested that IDO was only present mammals. However, recent phylogenic studies show that IDO paralogues are present within the whole vertebrate linage, however, their involvement in the immune and stress reaction in teleost fishes remains to be investigated. In this review we summarize the results from previous studies on the effects of dietary Trp supplementation on behavior and neuroendocrinology, focusing on possible mechanisms involved in mediating these effects.

  • 5. Morales Drissi, Natasha
    et al.
    Romu, Thobias
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (IKE), Linköping University, Linköping, Sweden.
    Szakács, Attilla
    Hallböök, Tove
    Darin, Niklas
    Borga, Magnus
    Leinhard, Olof Dahlqvist
    Engström, Maria
    Unexpected Fat Distribution in Adolescents With Narcolepsy.2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 728Article in journal (Refereed)
    Abstract [en]

    Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease.

  • 6. Nässel, Dick R
    et al.
    Williams, Michael J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cholecystokinin-Like Peptide (DSK) in Drosophila, Not Only for Satiety Signaling2014In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 5, p. 219-Article in journal (Refereed)
    Abstract [en]

    Cholecystokinin (CCK) signaling appears well conserved over evolution. In Drosophila, the CCK-like sulfakinins (DSKs) regulate aspects of gut function, satiety and food ingestion, hyperactivity and aggression, as well as escape-related locomotion and synaptic plasticity during neuromuscular junction development. Activity in the DSK-producing neurons is regulated by octopamine. We discuss mechanisms behind CCK function in satiety, aggression, and locomotion in some detail and highlight similarities to mammalian CCK signaling.

  • 7.
    Ritze, Yvonne
    et al.
    Univ Tubingen, Dept Med Psychol & Behav Neurobiol, Tubingen, Germany.
    Kern, Werner
    Endokrinologikum Ulm, Ulm, Germany.
    Ebner, Eva-Maria
    Univ Tubingen, Dept Med Psychol & Behav Neurobiol, Tubingen, Germany;Univ Lubeck, Dept Internal Med 1, Lubeck, Germany.
    Jahn, Serena
    Univ Tubingen, Dept Med Psychol & Behav Neurobiol, Tubingen, Germany;Univ Lubeck, Dept Internal Med 1, Lubeck, Germany.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hallschmid, Manfred
    Univ Tubingen, Dept Med Psychol & Behav Neurobiol, Tubingen, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Tubingen IDM, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany.
    Metabolic and Cognitive Outcomes of Subchronic Once-Daily Intranasal Insulin Administration in Healthy Men2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 663Article in journal (Refereed)
    Abstract [en]

    Insulin acts in the brain to limit food intake and improve memory function. We have previously shown that 8 weeks of intranasal insulin delivered in four daily doses of 40 IU decrease body weight and enhance word list recall. In the present study, we investigated the effect on body composition, endocrine parameters, and memory performance of 8 weeks of once-daily administration of 160 IU in healthy men. We assumed that intranasal insulin administered before nocturnal sleep, a period of relative metabolic inactivity that moreover benefits memory formation, would be superior to insulin delivery in the morning and placebo administration. After a 2-week baseline period, healthy male normal-weight subjects (mean age, 27.1 +/- 0.9 years) received either placebo, 160 IU intranasal insulin in the morning, or 160 IU in the evening (n = 12 per group) for 8 consecutive weeks. Throughout the experiment, we measured body weight and body composition as well as circulating concentrations of glucose, insulin, adrenocorticotropin, cortisol, growth hormone, insulin-like growth-factor 1, adiponectin, and leptin. Declarative and procedural memory function was repeatedly assessed by means of, respectively, word list recall and word-stem priming. We found that neither morning nor evening insulin compared to placebo administration induced discernible changes in body weight and body composition. Delayed recall of words showed slight improvements by insulin administration in the evening, and serum cortisol concentrations were reduced after 2 weeks of insulin administration in the morning compared to the other groups. Results indicate that catabolic long-term effects of central nervous insulin delivery necessitate repetitive, presumably pre-meal delivery schedules. The observed memory improvements, although generally weaker than previously found effects, suggest that sleep after intranasal insulin administration may support its beneficial cognitive impact.

  • 8.
    Rodriguez-Raecke, Rea
    et al.
    Rhein Westfal TH Aachen, Diagnost & Intervent Neuroradiol, Univ Hosp, Aachen, Germany;Fraunhofer Inst Proc Engn & Packaging IW, Sensory Analyt, Freising Weihenstephan, Germany.
    Brünner, Yvonne F.
    Rhein Westfal TH Aachen, Diagnost & Intervent Neuroradiol, Univ Hosp, Aachen, Germany.
    Kofoet, Anja
    Rhein Westfal TH Aachen, Diagnost & Intervent Neuroradiol, Univ Hosp, Aachen, Germany.
    Mutic, Smiljana
    Rhein Westfal TH Aachen, Diagnost & Intervent Neuroradiol, Univ Hosp, Aachen, Germany.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Freiherr, Jessica
    Rhein Westfal TH Aachen, Diagnost & Intervent Neuroradiol, Univ Hosp, Aachen, Germany;Fraunhofer Inst Proc Engn & Packaging IW, Sensory Analyt, Freising Weihenstephan, Germany.
    Odor Sensitivity After Intranasal Insulin Application Is Modulated by Gender2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 580Article in journal (Refereed)
    Abstract [en]

    Obesity constitutes a global health care problem, and often eating habits are to blame. For intervention, a thorough understanding of energy intake and expenditure is needed. In recent years, the pivotal role of insulin in connection to energy intake was established. Olfactory sensitivity may be a target of cerebral insulin action to maintain body weight. With this experiment, we aimed to explore the influence of intranasal insulin on olfactory sensitivity for the odors n-butanol and peanut in a placebo-controlled, double-blind setting in a within-subject design. All subjects participated in two experimental sessions on separate days and received either intranasal insulin or placebo in a pseudorandomized order. Application was followed by two olfactory threshold tests for n-butanol and peanut in a pseudorandomized order. After a single dose of intranasal insulin (40 IU) or placebo (0.4 ml), olfactory sensitivity for the odorants n-butanol and peanut were examined in 30 healthy normosmic participants (14 females). Measured blood parameters revealed no decrease in plasma glucose, however, insulin, leptin and cortisol levels were affected following intranasal application. Females' but not males' olfactory sensitivity for n-butanol was lower after intranasal insulin administration vs. placebo. In contrast, olfactory sensitivity for peanut was not influenced by intranasal insulin application. Our results indicate that the effects of cortical insulin levels on processing of specific odors is likely modulated by gender, as central increase of insulin concentration led to a reduced olfactory sensitivity for n-butanol in women only, which might be due to differentially regulated insulin and leptin signaling in men and women.

  • 9.
    Titova, Olga E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Elmstahl, Solve
    Lund Univ, CRC, Dept Hlth Sci, Div Geriatr Med,Skane Univ Hosp, Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    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.
    Associations Between the Prevalence of Metabolic Syndrome and Sleep Parameters Vary by Age2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 234Article in journal (Refereed)
    Abstract [en]

    Objective: To examine whether the relationship between the metabolic syndrome (MetS) and various sleep parameters [sleep duration, symptoms of sleep-disordered breathing (SDB), and sleep disturbances] varies by age. Methods: Waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting glucose were used to determine MetS status in a cohort (N = 19,691) of middle-aged (aged 45-64 years) and older (aged >= 65 years) subjects. Habitual sleep duration (short, <= 6 h/day; normal, 7-8 h/day; and long >= 9 h/day), sleep disturbances (such as problems with falling and staying asleep), and symptoms of sleep-disordered breathing (SDB, such as snoring and sleep apneas) were measured by questionnaires. Results: Among the participants, 4,941 subjects (25.1%) fulfilled the criteria for MetS. In the entire sample, both short and long sleep durations were associated with higher prevalence of MetS as compared to normal sleep duration. When stratified by age, a similar pattern was observed for middle-aged subjects (<65 years old; prevalence ratio (PR) [95% CI], 1.13 [1.06-1.22] for short sleep and 1.26 [1.06-1.50] for long sleep duration). In contrast, in older individuals (>= 65 years old), only long sleep duration was linked to a higher prevalence of MetS (1.26 [1.12-1.42]; P < 0.01 for sleep duration x age). In the entire cohort, having at least one SDB symptom >= 4 times per week was linked to an increased prevalence of MetS; however, the PR was higher in middle-aged subjects compared with older subjects (1.50 [1.38-1.63] vs. 1.36 [1.26-1.47], respectively; P < 0.001 for SDB x age). Finally, independent of subjects' age, reports of sleep disturbances (i.e., at least one symptom >= 4 times per week) were associated with a higher likelihood of having MetS (1.12 [1.06-1.18]; P > 0.05 for sleep disturbance x age). Conclusion: Our results suggest that age may modify the associations between some sleep parameters and the prevalence of MetS.

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