HIV-1 Infection and the PPARγ-Dependent Control of Adipose Tissue Physiology

PPAR γ is a ligand-dependent master transcription factor controlling adipocyte differentiation as well as multiple biological processes taking place in other cells present in adipose tissue depots such as macrophages. Recent research indicates that HIV-1 infection-related events may alter adipose tissue biology through several mechanisms involving PPAR γ , ranging from direct effects of HIV-1-encoded proteins on adipocytes to the promotion of a proinflammatory environment that interferes with PPAR γ actions. This effect of HIV-1 on adipose tissue cells can occur even in the absence of direct infection of adipocytes, as soluble HIV-1-encoded proteins such as Vpr may enter cells and inhibit PPAR γ action. Moreover, repression of PPAR γ actions may relieve inhibitory pathways of HIV-1 gene transcription, thus enhancing HIV-1 effects in infected cells. HIV-1 infection-mediated interference of PPAR γ -dependent pathways in adipocytes and other cells inside adipose depots such as macrophages is likely to create an altered local environment that, after antiretroviral treatment, leads to lipodystrophy in HIV-1-infected and HAART-treated patients.