title: FGF21 mediates alcohol-induced adipose tissue lipolysis by activation of systemic release of catecholamine in mice.
abstract: Alcohol consumption leads to adipose tissue lipoatrophy and mobilization of FFAs, which contributes to hepatic fat accumulation in alcoholic liver disease. This study aimed to investigate the role of fibroblast growth factor (FGF)21, a metabolic regulator, in the regulation of chronic-binge alcohol-induced adipose tissue lipolysis. FGF21 KO mice were subjected to chronic-binge alcohol exposure, and epididymal white adipose tissue lipolysis and liver steatosis were investigated. Alcohol exposure caused adipose intracellular cAMP elevation and activation of lipolytic enzymes, leading to FFA mobilization in both WT and FGF21 KO mice. However, alcohol-induced systemic elevation of catecholamine, which is known to be a major player in adipose lipolysis by binding to the β-adrenergic receptor, was markedly inhibited in KO mice. Supplementation with recombinant human FGF21 to alcohol-exposed FGF21 KO mice resulted in an increase in fat loss in parallel with an increase of circulating norepinephrine concentration. Furthermore, alcohol consumption-induced fatty liver was blunted in the KO mice, indicating an inhibition of fatty acid reverse transport from adipose to the liver in the KO mice. Taken together, our studies demonstrate that FGF21 KO mice are protected from alcohol-induced adipose tissue excess-lipolysis through a mechanism involving systemic catecholamine release.
authors.affiliation: College of Basic Medical Sciences, Jilin University, Changchun, China Departments of Medicine University of Louisville School of Medicine, Louisville, KY Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Departments of Medicine University of Louisville School of Medicine, Louisville, KY Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Departments of Medicine University of Louisville School of Medicine, Louisville, KY Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Liming
authors.initials: L
authors.lastname: Liu
authors.affiliation: Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY.
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, New York University School of Medicine, New York, NY.
authors.forename: Moosa
authors.initials: M
authors.lastname: Mohammadi
authors.affiliation: Departments of Medicine University of Louisville School of Medicine, Louisville, KY Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY Robley Rex Veterans Administration Medical Center, Louisville, KY.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.affiliation: College of Basic Medical Sciences, Jilin University, Changchun, China School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Departments of Medicine University of Louisville School of Medicine, Louisville, KY Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D063425:Binge Drinking / Q000378:metabolism / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism*; D004822:Epididymis; D000431:Ethanol / Q000009:adverse effects*; D005235:Fatty Liver, Alcoholic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002395:Catecholamines; D007328:Insulin; C414620:fibroblast growth factor 21; D000431:Ethanol; D005346:Fibroblast Growth Factors
keywords: adipose tissue; alcoholic liver disease; cell signaling; fibroblast growth factor 21; lipolysis and fatty acid metabolism; liver