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FGF21 mediates alcohol-induced adipose tissue lipolysis by activation of systemic release of catecholamine in mice
Authors:Cuiqing Zhao  Yanlong Liu  Jian Xiao  Liming Liu  Shaoyu Chen  Moosa Mohammadi  Craig J McClain  Xiaokun Li  Wenke Feng
Institution:2. Departments of Medicine University of Louisville School of Medicine, Louisville, KY;4. Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY;11. Department of Pharmacology, New York University School of Medicine, New York, NY;8. Robley Rex Veterans Administration Medical Center, Louisville, KY
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.
Keywords:adipose tissue  lipolysis and fatty acid metabolism  liver  cell signaling  alcoholic liver disease  fibroblast growth factor 21
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