Plasma adiponectin in non alcoholic fatty liver disease is related to hepatic insulin resistance and hepatic fat content

Background and Aims: Plasma levels of adiponectin are decreased in patients with Nonalcoholic Fatty Liver Disease (NAFLD), but the relationship between plasma adiponectin, insulin sensitivity and histological features is unclear. Methods: We examined plasma adiponectin concentration in relation to ~/) indices of insulin resistance/sensitivity (HOMA-R, QUICKI, OGIS) and features of the metabolic syndrome in 179 NAFLD subjects, and hepatic insulin resistance (euglycemic hyperinsulinemic clamp technique with tracer infusion) in a subgroup of 10 NAFLD patients, and b) histological features at liver biopsy. Results: Adiponectin levels were sig-nificantly reduced in NAFLD patients compared with control subjects (5.94:t:2.70 vs 10.7:t:5.89~tg]ml; P <0.0001). A significant correlation was observed between indices of insulin resistance/sensitivity (HOMA-R and OGIS) and adiponectin levels in healthy subjects (r=-0.426; P = 0.007 and r= 0.232, P = 0.004, respectively), but not in NAFLD patients. Plasma adiponectin concentration significantly decreases with increasing number of positive criteria of metabolic syndrome (P=0.0067) and inversely correlate with insulinsuppressed EGP during the clamp (P=0.011). An inverse association is observed between adiponectin levels, ALT values and percent hepatic fat (P = 0.013 and 0.017 respectively). In multivariate analysis, after correction for age, gender and BMI, percent hepatic fat is the only predictive variable of plasma adiponectin in NAFLD (R2=0.048, P=0.0168). Conclusions: Decreased levels of circulating adiponectin in NAFLD are closely related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinernia in NAFLD is tightly associated with the metabolic syndrome, possibly as part of a metabolic disturbance characterized by ectopic fat accumulation and abnormal secretion of adypokines.