SIV Infection and the HIV Proteins Tat and Nef Induce Senescence in Adipose Tissue and Human Adipose Stem Cells, Resulting in Adipocyte Dysfunction.

Autor: Gorwood J; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France., Ejlalmanesh T; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France., Bourgeois C; Immunology of Viral infections and Autoimmune Diseases, IDMIT Department, IBFJ, U1184, INSERM -CEA-Université Paris Sud 11, F-92260 Fontenay-Aux-Roses and F-94270 Le Kremlin-Bicêtre, France., Mantecon M; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France., Rose C; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France., Atlan M; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France.; Plastic Surgery Department, Tenon Hospital, AP-HP, F-75020 Paris, France., Desjardins D; IDMIT Department, Center for Immunology of Viral Infections and Autoimmune Diseases, Inserm, CEA, Université Paris Saclay, F-92260 Fontenay-aux-Roses, France., Le Grand R; IDMIT Department, Center for Immunology of Viral Infections and Autoimmune Diseases, Inserm, CEA, Université Paris Saclay, F-92260 Fontenay-aux-Roses, France., Fève B; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France.; Diabétologie et Reproduction, PRISIS, Service d'Endocrinologie, Hôpital Saint-Antoine, AP-HP, F-75012 Paris, France., Lambotte O; Immunology of Viral infections and Autoimmune Diseases, IDMIT Department, IBFJ, U1184, INSERM -CEA-Université Paris Sud 11, F-92260 Fontenay-Aux-Roses and F-94270 Le Kremlin-Bicêtre, France.; Service de Médecine Interne et Immunologie Clinique, Groupe Hospitalier Universitaire Paris Sud, Hôpital Bicêtre, AP-HP, F-94270 Le Kremlin-Bicêtre, France., Capeau J; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France., Béréziat V; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France., Lagathu C; Lipodystrophies, Metabolic and Hormonal Adaptation, and Aging, UMR_S 938, Centre de Recherche Saint-Antoine-Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), INSERM, Sorbonne Université, F-75012 Paris, France.
Jazyk: angličtina
Zdroj: Cells [Cells] 2020 Apr 01; Vol. 9 (4). Date of Electronic Publication: 2020 Apr 01.
DOI: 10.3390/cells9040854
Abstrakt: Background: Aging is characterized by adipose tissue senescence, inflammation, and fibrosis, with trunk fat accumulation. Aging HIV-infected patients have a higher risk of trunk fat accumulation than uninfected individuals-suggesting that viral infection has a role in adipose tissue aging. We previously demonstrated that HIV/SIV infection and the Tat and Nef viral proteins were responsible for adipose tissue fibrosis and impaired adipogenesis. We hypothesized that SIV/HIV infection and viral proteins could induce adipose tissue senescence and thus lead to adipocyte dysfunctions.
Methods: Features of tissue senescence were evaluated in subcutaneous and visceral adipose tissues of SIV-infected macaques and in human adipose stem cells (ASCs) exposed to Tat or Nef for up to 30 days.
Results: p16 expression and p53 activation were higher in adipose tissue of SIV-infected macaques than in control macaques, indicating adipose tissue senescence. Tat and Nef induced higher senescence in ASCs, characterized by higher levels of senescence-associated beta-galactosidase activity, p16 expression, and p53 activation vs. control cells. Treatment with Tat and Nef also induced oxidative stress and mitochondrial dysfunction. Prevention of oxidative stress (using N-acetyl-cysteine) reduced senescence in ASCs. Adipocytes having differentiated from Nef-treated ASCs displayed alterations in adipogenesis with lower levels of triglyceride accumulation and adipocyte marker expression and secretion, and insulin resistance.
Conclusion: HIV/SIV promotes adipose tissue senescence, which in turn may alter adipocyte function and contribute to insulin resistance.
Databáze: MEDLINE
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