High adiponectin in chronic liver disease and cholestasis suggests biliary route of adiponectin excretion in vivo

Background/Aims Models of fatty liver diseases and fibrosis suggest a hepatoprotective effect of adiponectin, an adipocyte-derived hormone with antidiabetic, antiobesity, antiatherogenic and anti-inflammatory effects. Methods We studied adiponectin serum levels in 111 chronic liver disease (CLD) patients and 226 healthy controls and the impact of cholestasis on adiponectin by bile duct ligation experiments in mice. Results Adiponectin was significantly elevated in CLD, and correlated with stage of liver cirrhosis, liver cell injury, e.g. aminotransferase activity, and inflammatory markers, but not with liver synthesis capacity, insulin sensitivity (HOMA index) or clinical complications. As patients with biliary liver diseases and cholestasis exhibited the highest adiponectin levels, we experimentally investigated a potential biliary route of adiponectin excretion. Following bile duct ligation in mice adiponectin levels rapidly increased without affecting hepatic adiponectin gene expression. Also, adiponectin was detectable in human bile. High adiponectin concentrations were associated with severe cholangitis and/or cholestasis on liver histology. Conclusions Adiponectin is elevated in chronic liver disease and correlates with inflammation and liver damage. High adiponectin levels after bile duct ligation in mice and in human bile from cholestatic patients suggest that biliary secretion is involved in adiponectin clearance and that adiponectin could serve as a novel marker indicating cholestasis in liver cirrhosis.