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Alsiö, Johan
Publications (10 of 23) Show all publications
Feltmann, K., Giuliano, C., Everitt, B. J., Steensland, P. & Alsiö, J. (2018). The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats. Neuropsychopharmacology, 43(3), 617-626
Open this publication in new window or tab >>The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats
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2018 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 617-626Article in journal (Refereed) Published
Abstract [en]

Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre-and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-341560 (URN)10.1038/npp.2017.215 (DOI)000419961500018 ()28895569 (PubMedID)
Funder
Swedish Society of Medicine, SLS-253061Wellcome trustSwedish Research Council, 350-2012-230, 2015-03525Swedish Society for Medical Research (SSMF)
Available from: 2018-02-14 Created: 2018-02-14 Last updated: 2018-02-14Bibliographically approved
Zhukovsky, P., Alsiö, J., Jupp, B., Xia, J., Giuliano, C., Jenner, L., . . . Dalley, J. W. (2017). Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels. Psychopharmacology, 234(9-10), 1557-1571
Open this publication in new window or tab >>Perseveration in a spatial-discrimination serial reversal learning task is differentially affected by MAO-A and MAO-B inhibition and associated with reduced anxiety and peripheral serotonin levels
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2017 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 234, no 9-10, p. 1557-1571Article in journal (Refereed) Published
Abstract [en]

Impairments in behavioral flexibility lie at the core of anxiety and obsessive-compulsive disorders. Few studies, however, have investigated the neural substrates of natural variation in behavioral flexibility and whether inflexible behavior is linked to anxiety and peripheral markers of stress and monoamine function. The objective of the study was to investigate peripheral and central markers associated with perseverative behavior on a spatial-discrimination serial reversal learning task. Rats were trained on a reversal learning task prior to blood sampling, anxiety assessment, and the behavioral evaluation of selective monoamine oxidase-A (MAO-A) and MAO-B inhibitors, which block the degradation of serotonin (5-HT), dopamine (DA), and noradrenaline (NA). Perseveration correlated positively with 5-HT levels in blood plasma and inversely with trait anxiety, as measured on the elevated plus maze. No significant relationships were found between perseveration and the stress hormone corticosterone or the 5-HT precursor tryptophan. Reversal learning was significantly improved by systemic administration of the MAO-A inhibitor moclobemide but not by the MAO-B inhibitor lazabemide. Moclobemide also increased latencies to initiate a new trial following an incorrect response suggesting a possible role in modulating behavioral inhibition to negative feedback. MAO-A but not MAO-B inhibition resulted in pronounced increases in 5-HT and NA content in the orbitofrontal cortex and dorsal raph, nuclei and increased 5-HT and DA content in the basolateral amygdala and dorsomedial striatum. These findings indicate that central and peripheral monoaminergic mechanisms underlie inter-individual variation in behavioral flexibility, which overlaps with trait anxiety and depends on functional MAO-A activity.

Place, publisher, year, edition, pages
SPRINGER, 2017
Keywords
Behavioral flexibility, Moclobemide, Lazabemide, Endophenotype, Orbitofrontal cortex, Basolateral amygdala, Striatum
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-324627 (URN)10.1007/s00213-017-4569-x (DOI)000400855400019 ()28251298 (PubMedID)
Available from: 2017-06-19 Created: 2017-06-19 Last updated: 2018-02-22Bibliographically approved
Pickering, C., Alsiö, J., Morud, J., Ericson, M., Robbins, T. W. & Soderpalm, B. (2015). Ethanol impairment of spontaneous alternation behaviour and associated changes in medial prefrontal glutamatergic gene expression precede putative markers of dependence. Pharmacology, Biochemistry and Behavior, 132, 63-70
Open this publication in new window or tab >>Ethanol impairment of spontaneous alternation behaviour and associated changes in medial prefrontal glutamatergic gene expression precede putative markers of dependence
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2015 (English)In: Pharmacology, Biochemistry and Behavior, ISSN 0091-3057, E-ISSN 1873-5177, Vol. 132, p. 63-70Article in journal (Refereed) Published
Abstract [en]

Cognitive impairments are observable in over half of cases with alcoholism, deficits in spatial working memory being particularly common. Previously we observed that rats make more alternation errors in a Y-maze test of spontaneous alternation behaviour/spatial working memory after 5-day intermittent ethanol. Here we used qPCR to quantify changes in gene expression accompanying this behavioural impairment. Male Wistar rats were treated with either saline or ethanol (1 or 2.5 g/kg) for 5 days followed by 2 drug-free days. Brains were dissected after Y-maze analysis and RNA was extracted from the medial prefrontal cortex, hippocampus and nucleus accumbens. Using the Qiagen GABA & Glutamate PCR array we measured changes in these two neurotransmitter systems. A dose of 1 g/kg ethanol did not affect spontaneous alternation behaviour or any other behavioural variable. 2.5 g/kg significantly decreased % correct alternations (p = 0.028) without affecting total distance (p = 0.54) and increased time in the choice area (p = 0.023) at the Y-maze centre, indicating a possible impairment in decision-making. In the medial prefrontal cortex, 2.5 g/kg ethanol decreased mRNA expression of brain-derived neurotrophic factor, NMDA NR2A subunit, mGluR8 receptor, Homer1, the glutamate transporters SLC1a1 and SLC1a6 and Srr. In the nucleus accumbens this dose did not affect mRNA expression of the dopamine D1 or D2 receptors but did upregulate the GABA transporter GAT-3. Even if only correlational, these data suggest that gene expression changes in the medial prefrontal cortex and associated cognitive impairment occur before adaptation of the dopaminergic system and, presumably, drug dependence.

Keywords
Alcoholism, Cognitive impairment, GABA, Dopamine, qPCR
National Category
Neurosciences Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-253242 (URN)10.1016/j.pbb.2015.02.021 (DOI)000353860800008 ()
Available from: 2015-06-17 Created: 2015-05-25 Last updated: 2018-01-11Bibliographically approved
Barlow, R. L., Alsiö, J., Jupp, B., Rabinovich, R., Shrestha, S., Roberts, A. C., . . . Dalley, J. W. (2015). Markers of Serotonergic Function in the Orbitofrontal Cortex and Dorsal Raphe Nucleus Predict Individual Variation in Spatial-Discrimination Serial Reversal Learning. Neuropsychopharmacology, 40(7), 1619-1630
Open this publication in new window or tab >>Markers of Serotonergic Function in the Orbitofrontal Cortex and Dorsal Raphe Nucleus Predict Individual Variation in Spatial-Discrimination Serial Reversal Learning
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2015 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 40, no 7, p. 1619-1630Article in journal (Refereed) Published
Abstract [en]

Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid-and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphe nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low-vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior.

National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-255058 (URN)10.1038/npp.2014.335 (DOI)000354321600007 ()25567428 (PubMedID)
Available from: 2015-06-22 Created: 2015-06-12 Last updated: 2018-01-11Bibliographically approved
Caruso, V., Le Greves, M., Fard, S. S., Haitina, T., Olszewski, P. K., Alsiö, J., . . . Fredriksson, R. (2015). The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake. PLoS ONE, 10(6), Article ID e0122061.
Open this publication in new window or tab >>The Orphan G Protein-Coupled Receptor Gene GPR178 Is Evolutionary Conserved and Altered in Response to Acute Changes in Food Intake
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0122061Article in journal (Refereed) Published
Abstract [en]

G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating physiological functions fundamental for survival, including energy homeostasis. A few years ago, an amino acid sequence of a novel GPCR gene was identified and named GPR178. In this study, we provide new insights regarding the biological significance of Gpr178 protein, investigating its evolutionary history and tissue distribution as well as examining the relationship between its expression level and feeding status. Our phylogenetic analysis indicated that GPR178 is highly conserved among all animal species investigated, and that GPR178 is not a member of a protein family. Real-time PCR and in situ hybridization revealed wide expression of Gpr178 mRNA in both the brain and periphery, with high expression density in the hypothalamus and brainstem, areas involved in the regulation of food intake. Hence, changes in receptor expression were assessed following several feeding paradigms including starvation and overfeeding. Short-term starvation (12-48h) or food restriction resulted in upregulation of Gpr178 mRNA expression in the brainstem, hypothalamus and prefrontal cortex. Conversely, short-term (48h) exposure to sucrose or Intralipid solutions downregulated Gpr178 mRNA in the brainstem; long-term exposure (10 days) to a palatable high-fat and high-sugar diet resulted in a downregulation of Gpr178 in the amygdala but not in the hypothalamus. Our results indicate that hypothalamic Gpr178 gene expression is altered during acute exposure to starvation or acute exposure to palatable food. Changes in gene expression following palatable diet consumption suggest a possible involvement of Gpr178 in the complex mechanisms of feeding reward.

National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-257655 (URN)10.1371/journal.pone.0122061 (DOI)000355652200002 ()26047506 (PubMedID)
Funder
Swedish Research Council
Available from: 2015-07-07 Created: 2015-07-06 Last updated: 2018-01-11Bibliographically approved
Alsiö, J., Rask-Andersen, M., Chavan, R. A., Olszewski, P. K., Levine, A. S., Fredriksson, R. & Schiöth, H. B. (2014). Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats. Neuroscience Letters, 559, 18-23
Open this publication in new window or tab >>Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats
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2014 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 559, p. 18-23Article in journal (Refereed) Published
Abstract [en]

A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity.

Keywords
Obesity; Dopamine; Hindbrain; Brainstem; Pro-opiomelanocortin
National Category
Biological Sciences Neurology
Identifiers
urn:nbn:se:uu:diva-220149 (URN)10.1016/j.neulet.2013.11.008 (DOI)000331021900004 ()24262750 (PubMedID)
Funder
Swedish Research Council
Note

Delat första författarskap Johan Alsiö och Mathias Rask-Andersen.

Available from: 2014-03-11 Created: 2014-03-11 Last updated: 2017-12-05Bibliographically approved
Cedernaes, J., Alsiö, J., Västermark, Å., Risérus, U. & Schiöth, H. B. (2013). Adipose tissue stearoyl-CoA desaturase 1 index is increased and linoleic acid is decreased in obesity-prone rats fed a high-fat diet. Lipids in Health and Disease, 12(2)
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
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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
Alsiö, J., Olszewski, P. K., Levine, A. S. & Schiöth, H. B. (2012). Feed-forward mechanisms: Addiction-like behavioral and molecular adaptations in overeating. Frontiers in neuroendocrinology (Print), 33(2), 127-139
Open this publication in new window or tab >>Feed-forward mechanisms: Addiction-like behavioral and molecular adaptations in overeating
2012 (English)In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 33, no 2, p. 127-139Article, review/survey (Refereed) Published
Abstract [en]

Food reward, not hunger, is the main driving force behind eating in the modern obesogenic environment. Palatable foods, generally calorie-dense and rich in sugar/fat, are thus readily overconsumed despite the resulting health consequences. Important advances have been made to explain mechanisms underlying excessive consumption as an immediate response to presentation of rewarding tastants. However, our understanding of long-term neural adaptations to food reward that oftentimes persist during even a prolonged absence of palatable food and contribute to the reinstatement of compulsive overeating of high-fat high-sugar diets, is much more limited. Here we discuss the evidence from animal and human studies for neural and molecular adaptations in both homeostatic and non-homeostatic appetite regulation that may underlie the formation of a "feed-forward" system, sensitive to palatable food and propelling the individual from a basic preference for palatable diets to food craving and compulsive, addiction-like eating behavior.

Keywords
Obesity, Addiction, Craving, Plasticity, Dietary fat, Sugar
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-177891 (URN)10.1016/j.yfrne.2012.01.002 (DOI)000305817700001 ()
Available from: 2012-07-20 Created: 2012-07-20 Last updated: 2017-12-07Bibliographically approved
Wallen-Mackenzie, Å., Arvidsson, E., Restrepo, E., Johann, S. P., Perland, E., Nordenankar, K., . . . Leao, R. N. (2012). Targeting VGLUT2 in dopamine neurons affects the brain reward system. Paper presented at 25th Congress of the European-College-of-Neuropsychopharmacology (ECNP), OCT 13-17, 2012, Vienna, AUSTRIA. European Neuropsychopharmacology, 22(S2), S128-S129
Open this publication in new window or tab >>Targeting VGLUT2 in dopamine neurons affects the brain reward system
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2012 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no S2, p. S128-S129Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-200870 (URN)10.1016/S0924-977X(12)70155-4 (DOI)000317948600046 ()
Conference
25th Congress of the European-College-of-Neuropsychopharmacology (ECNP), OCT 13-17, 2012, Vienna, AUSTRIA
Available from: 2013-06-04 Created: 2013-06-04 Last updated: 2017-12-06Bibliographically approved
Mirza, M., Alsiö, J., Hammarstedt, A., Erben, R., Michaëlsson, K., Tivesten, Å., . . . Larsson, T. (2011). Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arteriosclerosis, Thrombosis and Vascular Biology, 31(1), 219-227
Open this publication in new window or tab >>Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals
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2011 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 31, no 1, p. 219-227Article in journal (Refereed) Published
Abstract [en]

Objective—Disturbances in mineral metabolism define an increased cardiovascular risk in patients with chronic kidney disease. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has recently been implicated as a putative pathogenic factor in cardiovascular disease. Because other members of the FGF family play a role in lipid and glucose metabolism, we hypothesized that FGF23 would associate with metabolic factors that predispose to an increased cardiovascular risk. The goal of this study was to investigate the relationship between FGF23 and metabolic cardiovascular risk factors in the community.

Methods and Results—Relationships between serum FGF23 and body mass index (BMI), waist circumference, waist-to-hip ratio, serum lipids, and fat mass were examined in 2 community-based, cross-sectional cohorts of elderly whites (Osteoporotic Fractures in Men Study: 964 men aged 75±3.2; Prospective Investigation of the Vasculature in Uppsala Seniors study: 946 men and women aged 70). In both cohorts, FGF23 associated negatively with high-density lipoprotein and apolipoprotein A1 (7% to 21% decrease per 1-SD increase in log FGF23; P<0.01) and positively with triglycerides (11% to 14% per 1-SD increase in log FGF23; P<0.01). A 1-SD increase in log FGF23 was associated with a 7% to 20% increase in BMI, waist circumference, and waist-to-hip ratio and a 7% to 18% increase in trunk and total body fat mass (P<0.01) as determined by whole-body dual x-ray absorptiometry. FGF23 levels were higher in subjects with the metabolic syndrome compared with those without (46.4 versus 41.2 pg/mL; P<0.05) and associated with an increased risk of having the metabolic syndrome (OR per 1-SD increase in log FGF23, 1.21; 95% CI, 1.04 to 1.40; P<0.05).

Conclusion—We report for the first time on associations between circulating FGF23, fat mass, and adverse lipid metabolism resembling the metabolic syndrome, potentially representing a novel pathway(s) linking high FGF23 to an increased cardiovascular risk.

Keywords
cardiovascular disease prevention, diabetes mellitus, elderly, epidemiology, FGF-23, FGF23, Fibroblast growth factor-23, growth factors, lipids, metabolism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-130337 (URN)10.1161/ATVBAHA.110.214619 (DOI)000285342400033 ()20966399 (PubMedID)
Available from: 2010-09-06 Created: 2010-09-06 Last updated: 2017-12-12Bibliographically approved
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