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: Cuiqing Zhao, Yanlong Liu, Jian Xiao, Liming Liu, Shaoyu Chen, Moosa Mohammadi, Craig J McClain, Xiaokun Li, Wenke Feng
• Journal: Journal of lipid research (J Lipid Res) Vol. 56 Issue 8 Pg. 1481-91 (Aug 2015) ISSN: 1539-7262 [Electronic] United States
• PMID: 26092866 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Catecholamines
• Insulin
• fibroblast growth factor 21
• Ethanol
• Fibroblast Growth Factors

Topics

• Adipose Tissue (drug effects, metabolism)
• Adipose Tissue, White (drug effects, metabolism)
• Animals
• Binge Drinking (metabolism, pathology)
• Catecholamines (metabolism)
• Epididymis
• Ethanol (adverse effects)
• Fatty Liver, Alcoholic (genetics, metabolism, pathology)
• Fibroblast Growth Factors (deficiency, genetics, metabolism, pharmacology)
• Gene Expression Regulation (drug effects)
• Gene Knockout Techniques
• Humans
• Insulin (metabolism)
• Lipolysis (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Signal Transduction (drug effects)