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

Gene Expr. 2018 May 18;18(2):103-113. doi: 10.3727/105221617X15093738210295. Epub 2017 Nov 2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adiponectin / metabolism*
  • Animals
  • Ethanol / toxicity
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic / metabolism*
  • Signal Transduction


  • Adiponectin
  • Ethanol
  • Fibroblast Growth Factors