title: Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity.
abstract: Plasma levels of adiponectin are decreased in patients with nonalcoholic fatty liver disease (NAFLD), but the relationship among plasma adiponectin, insulin sensitivity, and histological features is unclear. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentrations in relation to 1) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); 2) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and 3) 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 high-density lipoprotein levels, and negatively associated with waist circumference, body mass index, triglycerides, indices of insulin resistance, and aminotransferase levels, and also predicted the presence of the metabolic syndrome. In step-wise regression, increased age, female gender, waist circumference, triglyceride levels, and homeostasis model assessment independently associated with adiponectin (adjusted R(2), 0.329). In NAFLD, adiponectin was only associated with increased age, female gender, and triglycerides (adjusted R(2), 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 R(2), 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.
authors.affiliation: Division of Gastroenterology, University of Turin, Ospedale San Giovanni Battista, Corso Bramante 88, I-10126 Torino, Italy. ebugianesi@yahoo.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.forename: Rita
authors.initials: R
authors.lastname: Manini
authors.forename: Ester
authors.initials: E
authors.lastname: Vanni
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Rosaria
authors.initials: R
authors.lastname: de Iasio
authors.forename: Elena
authors.initials: E
authors.lastname: Gentilcore
authors.forename: Stefania
authors.initials: S
authors.lastname: Natale
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cassader
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Renato
authors.initials: R
authors.lastname: Pasquali
authors.forename: Giulio
authors.initials: G
authors.lastname: Marchesini
mesh_terms: D052242:Adiponectin; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology; D008875:Middle Aged; D012016:Reference Values
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D036341:Intercellular Signaling Peptides and Proteins