Endocrine Abstracts

HIV-1-infected patients under antirretroviral treatment develop the so-called ‘lipodystrophy syndrome’. It is characterized by peripheral lipoatrophy (face, limbs), visceral lipohypertrophy, and, sometimes abnormal accumulation of subcutaneous fat in specific sites, especially the dorso-cervical area. The abnormal fat distribution is associated with systemic alterations characteristic of the metabolic syndrome (dyslipidemia, insulin resistance). Drugs are importantly involved in the development of the syndrome, but studies of fat biopsies from HIV-1-infected patients that had not yet started treatment revealed that alterations in adipose tissue are already present in association with the infection. A major alteration in the patients is mitochondrial toxicity, evidenced by mitochondrial DNA depletion in fat. This is mainly due to some of the antiretroviral drugs. However, the mitochondrial DNA depletion found commonly in atrophic and hypertrophic areas makes unlikely that this alteration was responsible for the opposite behavior of fat at distinct anatomical sites. Enhanced expression of pro-inflammatory cytokines (TNFα, MCP-1) takes place in lipoatrophic areas, whereas, in hypertrophic sites, this alteration is either non-present (dorso-cervical lipomatosis) or it has a minor intensity (visceral fat). The pro-inflammatory status in subcutaneous areas prone to atrophy is associated with a repression of the expression of adipogenic genes, such as PPARgamma, and its metabolic target genes (GLUT4, lipoprotein lipase). This alteration in adipogenesis is absent in hypertrophic areas. It is likely that the pro-inflammatory induction was a first event in eliciting the anti-adipogenic profile in atrophic fat. Finally, the dorso-cervical hypertrophic areas have features reminiscent of lipomatosis (enhanced proliferation, lowered telomere length) and a distorted brown-to-white adipose tissue phenotype (expression of the brown fat marker gene UCP1). HIV-1 lipodsytrophy appears as a multifaceted alteration in which inflammatory and adipogenic alterations act locally in a differential manner, with overall systemic alterations being associated with the complex distribution of fat disturbances.

Declaration of funding

Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (Grant PI11/00376) and Red de SIDA).