Circulating concentration of adiponectin and its expression in subcutaneous adipose tissue in patients with highly active antiretroviral therapy-associated lipodystrophy.
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 resistant 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 micro g/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 resistance in these patients.
Sutinen
Jussi
J
Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Helsinki, Finland.
Korsheninnikova
Elena
E
Funahashi
Tohru
T
Matsuzawa
Yuji
Y
Nyman
Tuulikki
T
Yki-Järvinen
Hannele
H
D000005:Abdomen; D000199:Actins / Q000235:genetics; D052242:Adiponectin; D000273:Adipose Tissue / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001823:Body Composition; D002096:C-Peptide / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D015870:Gene Expression; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood* / Q000139:chemically induced*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014280:Triglycerides / Q000097:blood
D000199:Actins; D052242:Adiponectin; D002096:C-Peptide; D008076:Cholesterol, HDL; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D014280:Triglycerides