Pathophysiology of the HIV-Associated Lipodystrophy Syndrome

The widespread use of highly active antiretroviral therapy (HAART) has radically transformed the prognosis of HIV-infected patients in the developed countries. Unfortunately, a serious metabolic syndrome combining peripheral lipoatrohy, central adiposity, insulin resistance, and dyslipidemia has arisen in these individuals. The etiology of this heterogeneous syndrome named lipodystrophy syndrome (LDS) is multifactorial, but adipose tissue is very likely a key factor that contributes to several clinical or metabolic aspects of the syndrome. In peripheral adipose tissue, HAART may act on both preadipocytes and adipocytes to induce fat loss. Several components of the HAART regimen can inhibit preadipocyte differentiation, in particular through alterations in the expression and/or function of the transcription factor sterol responsive element binding protein-1c. In superficial mature adipocytes, HAART promotes insulin resistance and apoptosis. Insulin resistance of peripheral fat cells could be the consequence of increased lipolysis and adipocytokine dysregulation. In turn, the increased free fatty acid disposal and the disturbances in adipocytokine production may induce skeletal muscle and liver insulin resistance, dyslipidemia, and a fat redistribution toward deep depots, causing visceral lipohypertrophy. The metabolic profile observed in LDS is reminiscent of that observed in metabolic syndrome, raising potential implications for cardiovascular risk in these patients. The pathophysiological mechanisms at the basis of this syndrome represent a rational basis for the treatment or prevention of the metabolic complications.