Subcutaneous Adipocyte Adenosine Triphosphate Levels in HIV Infected Patients.

Abstract

Lipoatrophy, or fat wasting, remains a syndrome plaguing HIV+ patients receiving antiretroviral (ARV) therapy. Both HIV infection per se and certain ARV are associated with lowered adipose tissue mitochondrial deoxyribonucleic acid (mtDNA) and mitochondrial ribonucleic acid (mtRNA) levels, but effects on adenosine triphosphate (ATP) production are unclear. We hypothesized that such alterations would accompany lowering of ATP levels in fat of HIV+ patients and would be worse in those displaying lipoatrophy. Gluteal-fold, subcutaneous adipose tissue was obtained from HIV seronegative control patients, from HIV+ ARV-naive patients, and those on ARV with or without lipoatrophy. Cellular ATP was measured in isolated adipocytes and preadipocyte fraction cells by bioluminescence. mtDNA copies/cell and oxidative phosphorylation (OXPHOS) mtRNA transcripts were evaluated by quantitative polymerase chain reactions. ATP levels were consistently higher in preadipocyte fraction cells than adipocytes, but values strongly correlated with each other (r = 0.66, p < .001). ATP levels in adipocytes were higher in both ARV-naive and nonlipoatrophic HIV+ patients compared to seronegative controls, but significantly lower in adipocytes and preadipocytes of lipoatrophic versus other HIV+ patients. Fat mtDNA copies/cell and OXPHOS mtRNA transcripts were lower in lipoatrophic patient samples compared to HIV seronegative. The ratio of specific OXPHOS transcripts to each other was significantly higher in nonlipoatrophic patients versus all groups, and this ratio correlated significantly with ATP levels in adipocytes. Thus, HIV infection is associated with an increase in adipose tissue ATP stores. Decreases in adipose mtDNA and OXPHOS mtRNA are found in those with HIV on ARV; however, ATP level is effected only in patients displaying lipoatrophy.