HIV antiretroviral treatment alters adipokine expression and insulin sensitivity of adipose tissue in vitro and in vivo.
HIV-1-infected patients on antiretroviral therapy frequently develop a lipodystrophy syndrome, characterized by peripheral lipoatrophy and visceral fat redistribution associated with metabolic alterations including dyslipidemia and insulin resistance. Its pathophysiology remains unclear but the antiretroviral treatment, associating protease inhibitors (PIs) and nucleoside analogue inhibitors of the viral reverse transcriptase (NRTIs), plays a major role. Some antiretroviral molecules inhibit differentiation and induce insulin resistance and apoptosis in adipose cells both in vitro and in vivo. In vitro, PIs and NRTIs increase the expression and secretion of pro-inflammatory cytokines such as TNF alpha, IL-6 and L-1beta, which are involved in altered adipocyte functions and decrease that of adiponectin, a positive modulator of insulin sensitivity. Similar alterations are observed in fat and serum from HIV-1-infected lipodystrophic patients under antiviral treatment associating PIs and NRTIs. Altered adipokine secretion could result from patients' exposure to PIs and NRTIs and lead to altered adipocyte differentiation, insulin resistance and apoptosis, ultimately resulting in lipoatrophy. These disorders probably result in a decreased secretion of adiponectin and an increased release of free fatty acids by insulin-resistant adipose tissue. Therefore, they could be involved in whole body insulin resistance and metabolic alterations in lipodystrophic HIV-1-infected patients.
Lagathu
Claire
C
Inserm U.680 and IFR65, Université Pierre et Marie Curie, Faculté de Médecine Saint-Antoine, 27, rue Chaligny, 75571 Paris cedex 12, France.
Kim
Minji
M
Maachi
Mustapha
M
Vigouroux
Corinne
C
Cervera
Pascale
P
Capeau
Jacqueline
J
Caron
Martine
M
Bastard
Jean-Philippe
JP
D016475:3T3 Cells; D052242:Adiponectin; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000502:physiology*; D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; D019380:Anti-HIV Agents; D016207:Cytokines; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D018894:Reverse Transcriptase Inhibitors; D014409:Tumor Necrosis Factor-alpha