antiretroviral-related adipocyte dysfunction and lipodystrophy in hiv-infected patients alteration of the ppar-dependent pathwaysantiretroviral-related脂肪细胞功能障碍和脂肪代谢障碍在艾滋病病毒感染者ppar-dependent通路的改变.pdfVIP

Hindawi Publishing Corporation PPAR Research Volume 2009, Article ID 507141, 8 pages doi:10.1155/2009/507141 Review Article Antiretroviral-Related Adipocyte Dysfunction and Lipodystrophy in HIV-Infected Patients: Alteration of the PPARγ-Dependent Pathways Martine Caron,1, 2, 3 Corinne Vigouroux,1, 2, 3 Jean-Philippe Bastard,1, 2, 3 and Jacqueline Capeau1, 2, 3 1 Institut national de la sante et de la recherche medicale (Inserm), UMRS 893, 75012 Paris, France ´ ´ 2 Faculte de Medecine, Universite Pierre et Marie Curie (UPMC-Paris 6), 75012 Paris, France ´ ´ ´ 3 Assistance Publique - Hopitaux de Paris (AP-HP), Hopital Tenon, Service de Biochimie et Hormonologie, 75020 Paris, France ˆ ˆ Correspondence should be addressed to Jacqueline Capeau, jacqueline.capeau@inserm.fr Received 8 August 2008; Accepted 9 October 2008 Recommended by Lawrence Serfaty 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 PPARγ. Defective lamin A maturation linked to PI inhibitory activity could impede the nuclear translocation of SREBP1c, therefore, reducing PPARγ expression. Adipose cell function was partially restored by the PPARγ agonists, thiazolidinediones. Adverse effects of PIs and NRTIs have also been reported in macrophages, a cell type