Circulating Concentration of Adiponectin and Its Expression in Subcutaneous Adipose Tissue in Patients with Highly Active Antiretroviral Therapy-Associated Lipodystrophy

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 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.

Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

“…Patients with HAART-associated lipodystrophy have been shown to have low adiponectin gene expression in adipose tissue and low circulating adiponectin concentrations (41). Furthermore, low adiponectin has been shown to correlate inversely with liver fat in these patients (41). Thus, it can be speculated that inflammatory changes, such as those presented in the current study, may contribute to low adiponectin and high liver fat reported in this patient group.…”

“…In multiple human studies, changes in serum adiponectin induced by anti-diabetic agents of the thiazolidinedione class have been closely inversely correlated with those in liver fat (20). Patients with HAART-associated lipodystrophy have been shown to have low adiponectin gene expression in adipose tissue and low circulating adiponectin concentrations (41). Furthermore, low adiponectin has been shown to correlate inversely with liver fat in these patients (41).…”

Adiponectin: More Than Just Another Fat Cell Hormone?

“…Adipose tissue expression and circulating adiponectin concentrations have also been found to be significantly decreased in HIV-positive patients with lipodystrophy treated with highly active antiretroviral therapy. Both serum and mRNA concentrations of adiponectin were found to closely correlate with features of insulin resistance, including hepatic fat content (50). Thus, it may be reasonable to surmise that decreased production of adiponectin in lipoatrophic adipose tissue may contribute to the development of insulin resistance in these patients.…”

Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications

“…Thus adiponectin may be a better marker than leptin for insulin resistance seen in HIV subjects [89] . Taking these findings to the molecular level researchers have recently shown decreased adiponectin specific mRNA levels in fat biopsies from such lipodystrophic patients [90] . All the above results support the hypothesis that correction of adiponectin levels may ameliorate the metabolic changes observed in HIV patients.…”