The Role of Adipokines in HIV Lipodystrophy

Changes in body fat distribution are frequent findings in HIV/AIDS patients, with onset shortly after initiation of combination antiretroviral therapy (cART). Lipoatrophy (loss of peripheral subcutaneous fat from the face, arms, legs and buttocks, coupled with pronounced blood vessels in the arms and legs), can occur alone or in combination with lipohypertrophy (fat accumulation on the dorsocervical and abdominal regions). These changes are associated with diabetes and insulin resistance, metabolic abnormalities and increased risk of cardiovascular diseases.

The adipose tissue is now considered to be not only an energy storage organ, but also a metabolically-active endocrine organ that releases bioactive peptides (e.g., adipokines) into the bloodstream. Patients with lipodystrophy may experience marked changes in the circulating levels of adipocyte-secreted hormones, including adiponectin, leptin and resistin, to name a few. The role of adipocytokines in the pathogenesis of HIV-associated lipodystrophy is still not enough understood.

The most studied of adipokines, adiponectin expression is suppressed in obesity and diabetes, and inversely-correlated with insulin resistance and serum triglycerides. Previously published studies have shown that circulating adiponectin levels are lower in patients with chronic HIV infection accompanied by adipose tissue redistribution. Furthermore, in patients treated with cART, especially those with lipodystrophy, a gradual decrease of adiponectin levels has been noticed, coupled with a consecutive increase in cardiovascular risk.

On the other hand, the correlation between cART and leptin levels in HIV/AIDS patients is still up for debate. Recently published studies have either associated cART with lipodystrophy and hypoleptinemia, or denied an effect of cART on serum leptin levels.

Despite promising data from animal studies, the association of resistin with insulin resistance, diabetes or obesity has not been consistent in humans. Moreover, as part of a complex network of cART-related metabolic changes, elevated resistin levels have been reported in HIV/AIDS patients when compared to uninfected individuals.

The predictive value of changes in adipocytokine levels for adipose tissue redistribution and other connected metabolic disturbances should be evaluated in future studies to eventually enhance our understanding of the complex relations between HIV infection per se, drug-associated toxic effects, host genetic predisposition and several other factors participating and generating lipodystrophy and a subsequent development of the HIV metabolic syndrome.