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Submitted on November 15, 2004
Accepted on March 21, 2005
Division of Gastroenterology (E.B., E.V., E.G., M.R.) and Department of Internal Medicine (M.C.), Ospedale San Giovanni Battista, University of Turin, Turin, Italy; Endocrine Unit (U.P., R.D.I., R.P.), Center for Applied Biomedical Research, and Unit of Metabolic Diseases (R.M., S.N., G.M.), Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy; Metabolism Unit (A.G.), C.N.R. Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa, Pisa, Italy
* To whom correspondence should be addressed. E-mail: ebugianesi{at}yahoo.it.
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 concentrations 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 = 116).
When the data from all subjects were combined, plasma adiponectin levels were positively associated with increased age, female gender and plasma HDL levels, and negatively associated with waist circumference, BMI, triglycerides, indices of insulin resistance and aminotransferase levels, and also predicted the presence of the metabolic syndrome. In stepwise regression, increased age, female gender, waist circumference, triglyceride levels and HOMA-R resulted independently associated with adiponectin (adjusted R2, 0.329). In NAFLD, adiponectin was only associated with increased age, female gender and triglycerides (adjusted R2, 0.245). When the measured histological parameters were included in the model, plasma adiponectin levels were also inversely proportional to the percentage of hepatic fat content (adjusted R2, 0.221), whereas necroinflammation and fibrosis did not fit in the model. Adiponectin was negatively 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.
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