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Background:  Lipodystrophy is a major complication of HAART in HIV-infected patients, but the pathogenesis is still unclear. The lipin-deficient fld mouse resembles human patients with generalized lipodystrophy, having dramatically reduced adipose tissue stores throughout the body and insulin resistance. Recently, lipin has been shown to act in adipogenesis up-stream of the key transcriptional regulators PPAR-γ and C/EBP-α, such that lipin deficiency leads to impaired adipocyte differentiation in vitro and lipodystrophy in vivo. Here we investigate whether lipin expression in adipose tissue is altered in human HIV-associated lipodystrophy.

Methods:  HIV-infected patients with lipodystrophy (n = 17), without lipodystrophy (n = 17), and  healthy controls (n = 22), all men and age matched, participated in a cross-sectional study. HIV-infected patients were on successful and stable HAART. Biopsies were obtained from subcutaneous abdominal and femoral-gluteal adipose tissue after an overnight fast. Lipin mRNA expression was measured by real-time PCR and normalized to 18S. All subjects underwent a whole-body DEXA scan. HIV-infected patients had reduced total-, truncal- and limb-fat mass compared with healthy controls, and patients with lipodystrophy had more pronounced limb-fat loss than patients without lipodystrophy. Parametric statistical methods were used.

Results:  Lipin mRNA was expressed in adipose tissue in all groups. However, significantly lower expression levels were found in HIV patients with lipodystrophy compared with HIV patients without lipodystrophy in both adipose tissue compartments (abdominal region: geometric mean 1.10 [95% CI 0.78 to 1.56] vs 2.06 [1.30 to 3.24], p = 0.045; femoral-gluteal:  0.68 [0.43 to 1.05] vs 1.56 [0.98 to 2.50], p = 0.019]). Low lipin mRNA levels were associated with low percentage of limb fat mass (r = 0.65, p = 0.000) and high LDL-cholesterol (r = –0.41, p = 0.014).

Conclusions:  The findings of low levels of lipin mRNA in adipose tissue from HIV-infected patients with lipodystrophy and a strong association with limb fat loss suggest a mechanistic basis for lipin in HIV-associated lipodystrophy, and identify the lipin gene as a potential therapeutic target in the treatment of HIV-associated lipodystrophy.

Keywords: lipodystrophy; adipose tissue; lipin gene expression