Endocrine Adiponectin‐FGF15/19 Axis in Ethanol-Induced Inflammation and Alcoholic Liver Injury

Abstract

Alcoholic liver disease (ALD) is the most prevalent form of liver disease, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades, and exert similar beneficial functions. Emerging evidence has revealed that dysregulated adiponectin‐FGF15/19 axis and impaired hepatic adiponectin‐FGF15/19 signaling are associated with alcoholic liver damage in rodents and humans. More importantly, endocrine adiponectin‐FGF15/19 signaling confers protection against ethanol-induced liver damage via fine tuning the adipose‐intestine‐liver crosstalk, leading to limited hepatic inflammatory responses, and ameliorated alcoholic liver injury. This review is focused on the recently discovered endocrine adiponectin‐FGF15/19 axis that is emerging as an essential adipose‐gut‐liver coordinator involved in the development and progression of alcoholic steatohepatitis.