Department of Medicine, Divisions of Diabetes (J.S., H.Y.-J.) and Infectious Diseases (J.S.), Helsinki University Central Hospital, Helsinki, Finland; Minerva Research Institute (E.K., T.N.), Helsinki, Finland; and Department of Internal Medicine and Molecular Science (T.F., Y.M.), Osaka University Graduate School of Medicine, Osaka, Japan
Address correspondence to: Jussi Sutinen, M.D., Department of Medicine, University of Helsinki, P.O. Box 348, FIN-00029 Helsinki, Finland.
Abstract
Highly active antiretroviral therapy (HAART) has dramatically reduced HIV-related mortality, but is associated with severe metabolic adverse events, such as lipodystrophy and insulin resistance, the mechanisms of which are unknown. Adiponectin is a adipocytokine that is decreased in insulin reistant conditions. In mice, adiponectin decreases liver and muscle fat content and enhances insulin sensitivity. We determined serum adiponenctin and adiponectin mRNA concentrations in subcutaneous adipose tissue in HIV-positive HAART-treated patients with (HAART+LD+, n = 30) and without lipodystrophy (HAART+LD-, n = 13). The HAART+ LD+ group had significantly less subcutaneous and more intra-abdominal fat than the HAART+LD- group. Liver fat content (spectroscopy), serum insulin, C-peptide and triglyceride concentrations were significantly higher, and HDL cholesterol concentration lower in the HAART+LD+ than the HAART+LD- group. Serum adiponectin (3.4 ± 0.4 vs 8.5 ± 1.0 µg/mL, p < 0.001) and adiponectin mRNA concentration in subcutaneous adipose tissue (7 ± 1 x 10-4 vs 24 ± 6 x 10-4, p < 0.001) were significantly lower in the HAART+LD+ than the HAART+LD- group. Both serum adiponectin and mRNA concentrations correlated closely with features of insulin resistance, including liver fat content. These data suggest that the decreased production of adiponectin in lipoatrophic adipose tissue may contribute to hepatic insulin reistance in these patients.
Footnotes
1 J.S. and E.K. contributed equally to this work