title: Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling.
abstract: Retinoic acid, an active metabolite of dietary vitamin A, acts as a ligand for nuclear receptor transcription factors with more than 500 known target genes. It is becoming increasingly clear that alcohol has a significant impact on cellular retinoic acid metabolism, with resultant effects on its function. Here, we test the hypothesis that chronic alcohol consumption impairs retinoic acid signaling in brown adipose tissue (BAT), leading to impaired BAT function and thermoregulation. All studies were conducted in age-matched, male mice consuming alcohol-containing liquid diets. Alcohol's effect on BAT was assessed by histology, qPCR, HPLC, LC/MS and measures of core body temperature. Our data show that chronic alcohol consumption decreases BAT mass, with a resultant effect on thermoregulation. Follow-up mechanistic studies reveal a decreased triglyceride content in BAT, as well as impaired retinoic acid homeostasis, associated with decreased BAT levels of retinoic acid in alcohol-consuming mice. Our work highlights a hitherto uncharacterized effect of alcohol on BAT function, with possible implications for thermoregulation and energy metabolism in drinkers. Our data indicate that alcohol's effects on brown adipose tissue may be mediated through altered retinoic acid signaling.
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Madeleine A
authors.initials: MA
authors.lastname: Gao
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Timothy R A
authors.initials: TR
authors.lastname: Dalmer
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Xueyuan J
authors.initials: XJ
authors.lastname: Hu
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.|Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Robin D
authors.initials: RD
authors.lastname: Clugston
mesh_terms: D000217:Acyltransferases / Q000172:deficiency / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D004032:Diet / Q000379:methods; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D020033:Protein Isoforms; C000607072:Rara protein, mouse; D000072482:Retinoic Acid Receptor alpha; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014801:Vitamin A; D000431:Ethanol; D014212:Tretinoin; C000607081:Cyp26b1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; D000080924:Aldehyde Dehydrogenase 1 Family; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase