Min You and Christopher Q. Rogers
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Alcoholic fatty liver is a major risk factor for advanced liver injuries such as steatohepatitis, fibrosis, and cirrhosis. While the underlying mechanisms are multiple, the development of alcoholic fatty liver has been attributed to a combined increase in the rate of de novo lipogenesis and a decrease in the rate of fatty acid oxidation in animal liver. Among various transcriptional regulators, the hepatic SIRT1 (sirtuin 1)-AMPK (AMPK-activated kinase) signaling system represents a central target for the action of ethanol in the liver. Adiponectin is one of the adipocyte-derived adipokines with potent lipid-lowering properties. Growing evidence has demonstrated that the development of alcoholic fatty liver is associated with reduced circulating adiponectin levels, decreased hepatic adiponectin receptor expression, and impaired hepatic adiponectin signaling. Adiponectin confers protection against alcoholic fatty liver via modulation of complex hepatic signaling pathways largely controlled by the central regulatory system, SIRT1-AMPK axis. This review aims to integrate the current research findings of ethanol-mediated dysregulation of adiponectin and its receptors and to provide a comprehensive point of view for understanding the role of adiponectin signaling in the development of alcoholic fatty liver.
Figure 1. Proposed mechanisms that underlie the protective action of adiponectin against alcoholic fatty liver. Adiponectin protects against development of alcoholic fatty liver through coordination of multiple signaling pathways mediated by various transcriptional regulators including SIRT1, AMPK, SREBP-1, PGC-1 /PPAR , CD36, and UCP2. Abbreviations: AdipoR, adiponectin receptor; AMPK, AMP-activated kinase; ACC, acetyl-coenzyme A carboxylase; CD36, fatty-acid translocase; FA, free fatty acids; MRC, mitochondrial respiratory chain; SIRT1, sirtuin 1; SREBP-1c, sterol regulatory element-binding protein 1c; PGC-1 , peroxisome proliferator-activated receptor co-activator-alpha; PPAR , peroxisome proliferator-activated receptor alpha; TNF , tumor necrosis factor alpha; UCP2, uncoupling protein-2.
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