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PPAR Research
Volume 2009, Article ID 507141, 8 pages
http://dx.doi.org/10.1155/2009/507141
Review Article

Antiretroviral-Related Adipocyte Dysfunction and Lipodystrophy in HIV-Infected Patients: Alteration of the PPAR -Dependent Pathways

1Institut national de la santé et de la recherche médicale (Inserm), UMRS 893, 75012 Paris, France
2Faculté de Médecine, Université Pierre et Marie Curie (UPMC-Paris 6), 75012 Paris, France
3Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Tenon, Service de Biochimie et Hormonologie, 75020 Paris, France

Received 8 August 2008; Accepted 9 October 2008

Academic Editor: Lawrence Serfaty

Copyright © 2009 Martine Caron et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Lipodystrophy and metabolic alterations are major complications of antiretroviral therapy in HIV-infected patients. In vitro studies using cultured murine and human adipocytes revealed that some protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were implicated to a different extent in adipose cell dysfunction and that a chronic incubation with some PIs decreased mRNA and protein expression of PPAR . Defective lamin A maturation linked to PI inhibitory activity could impede the nuclear translocation of SREBP1c, therefore, reducing PPAR expression. Adipose cell function was partially restored by the PPAR agonists, thiazolidinediones. Adverse effects of PIs and NRTIs have also been reported in macrophages, a cell type that coexists with, and modulates, adipocyte function in fat tissue. In HIV-infected patients under ART, a decreased expression of PPAR and of PPAR -related genes was observed in adipose tissue, these anomalies being more severe in patients with ART-induced lipoatrophy. Altered PPAR expression was reversed in patients stopping PIs. Treatment of patients with agonists of PPAR could improve, at least partially, the subcutaneous lipoatrophy. These data indicate that decreased PPAR expression and PPAR -related function, resulting from ART-induced adipose tissue toxicity, play a central role in HIV-related lipoatrophy and metabolic consequences.