Plasma adiponectin in non alcoholic fatty liver disease is related to hepatic fat content and hepatic insulin resistance, not to liver disease severity

Abstract 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. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentration in relation to: a) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); b) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and c) histological features at liver biopsy (n = 114). In the whole group, plasma adiponectin levels were higher in females and were significantly associated with age, waist circumference, body mass index, lipid profile, insulin resistance and aminotransferase levels, and predicted the presence of the metabolic syndrome. In stepwise regression, only age, gender, waist circumference, triglycerides and HOMA-R were associated with adiponectin (adjusted R2, 0.329). In NAFLD, adiponectin was independently associated only with age, gender and triglycerides (adjusted R2, 0.245). When histology was added in the analysis, also percent hepatic fat was fit in the model (adjusted R2, 0.221), Histological parameters of necroinflammation and fibrosis were not associated with adiponectin. Adiponectin was inversely correlated with insulin-suppressed endogenous glucose production during the clamp (P = 0.011). The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinemia in NAFLD is part of a metabolic disturbance characterized by ectopic fat accumulation in the central compartment.