Jennifer Gorwood1, Christine Bourgeois2, Matthieu Mantecon1, Michael Atlan1,3, Valérie Pourcher4, Guillaume Pourcher5, Roger Le Grand2, Delphine Desjardins2, Bruno Fève1,6, Olivier Lambotte2,7, Jacqueline Capeau1, Véronique Béréziat1, Claire Lagathu1. 1. Sorbonne Université, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Paris. 2. CEA - Université Paris Sud 11 - Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, 92265 Fontenay-aux-Roses. 3. AP-HP, Hôpital Tenon, Service de Chirurgie Plastique et Esthétique. 4. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses et Tropicales, Sorbonne Université. 5. Institut Mutualiste Montsouris, Service de Chirurgie Digestive. 6. AP-HP, Hôpital Saint-Antoine, PRISIS, Service d'Endocrinologie, Diabétologie et Reproduction, Paris. 7. AP-HP, Groupe Hospitalier Universitaire Paris Sud, Hôpital Bicêtre, Service de Médecine Interne et Immunologie Clinique, Le Kremlin-Bicêtre, France.
Abstract
OBJECTIVE: HIV-infected patients receiving antiretroviral treatment (ART) often present adipose tissue accumulation and/or redistribution. adipose tissue has been shown to be an HIV/SIV reservoir and viral proteins as Tat or Nef can be released by infected immune cells and exert a bystander effect on adipocytes or precursors. Our aim was to demonstrate that SIV/HIV infection per se could alter adipose tissue structure and/or function. DESIGN: Morphological and functional alterations of subcutaneous (SCAT) and visceral adipose tissue (VAT) were studied in SIV-infected macaques and HIV-infected ART-controlled patients. To analyze the effect of Tat or Nef, we used human adipose stem cells (ASCs) issued from healthy donors, and analyzed adipogenesis and extracellular matrix component production using two dimensional (2D) and three-dimensional (3D) culture models. METHODS: Adipocyte size and index of fibrosis were determined on Sirius red-stained adipose tissue samples. Proliferating and adipocyte 2D-differentiating or 3D-differentiating ASCs were treated chronically with Tat or Nef. mRNA, protein expression and secretion were examined by RT-PCR, western-blot and ELISA. RESULTS: SCAT and VAT from SIV-infected macaques displayed small adipocytes, decreased adipogenesis and severe fibrosis with collagen deposition. SCAT and VAT from HIV-infected ART-controlled patients presented similar alterations. In vitro, Tat and/or Nef induced a profibrotic phenotype in undifferentiated ASCs and altered adipogenesis and collagen production in adipocyte-differentiating ASCs. CONCLUSION: We demonstrate here a specific role for HIV/SIV infection per se on adipose tissue fibrosis and adipogenesis, probably through the release of viral proteins, which could be involved in adipose tissue dysfunction contributing to cardiometabolic alterations of HIV-infected individuals.
OBJECTIVE:HIV-infectedpatients receiving antiretroviral treatment (ART) often present adipose tissue accumulation and/or redistribution. adipose tissue has been shown to be an HIV/SIV reservoir and viral proteins as Tat or Nef can be released by infected immune cells and exert a bystander effect on adipocytes or precursors. Our aim was to demonstrate that SIV/HIV infection per se could alter adipose tissue structure and/or function. DESIGN: Morphological and functional alterations of subcutaneous (SCAT) and visceral adipose tissue (VAT) were studied in SIV-infected macaques and HIV-infected ART-controlled patients. To analyze the effect of Tat or Nef, we used human adipose stem cells (ASCs) issued from healthy donors, and analyzed adipogenesis and extracellular matrix component production using two dimensional (2D) and three-dimensional (3D) culture models. METHODS: Adipocyte size and index of fibrosis were determined on Sirius red-stained adipose tissue samples. Proliferating and adipocyte 2D-differentiating or 3D-differentiating ASCs were treated chronically with Tat or Nef. mRNA, protein expression and secretion were examined by RT-PCR, western-blot and ELISA. RESULTS: SCAT and VAT from SIV-infected macaques displayed small adipocytes, decreased adipogenesis and severe fibrosis with collagen deposition. SCAT and VAT from HIV-infected ART-controlled patients presented similar alterations. In vitro, Tat and/or Nef induced a profibrotic phenotype in undifferentiated ASCs and altered adipogenesis and collagen production in adipocyte-differentiating ASCs. CONCLUSION: We demonstrate here a specific role for HIV/SIV infection per se on adipose tissue fibrosis and adipogenesis, probably through the release of viral proteins, which could be involved in adipose tissue dysfunction contributing to cardiometabolic alterations of HIV-infected individuals.
Authors: Sepiso K Masenga; Fernando Elijovich; John R Koethe; Benson M Hamooya; Douglas C Heimburger; Sody M Munsaka; Cheryl L Laffer; Annet Kirabo Journal: Curr Hypertens Rep Date: 2020-09-03 Impact factor: 5.369
Authors: Curtis L Gabriel; Fei Ye; Run Fan; Sangeeta Nair; James G Terry; John Jeffrey Carr; Heidi Silver; Paxton Baker; LaToya Hannah; Celestine Wanjalla; Mona Mashayekhi; Sam Bailin; Morgan Lima; Beverly Woodward; Manhal Izzy; Jane F Ferguson; John R Koethe Journal: Hepatol Commun Date: 2021-02-27