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Impact of HIV/simian immunodeficiency virus infection and viral proteins on adipose tissue fibrosis and adipogenesis

Gorwood, Jennifera; Bourgeois, Christineb; Mantecon, Matthieua; Atlan, Michaela,c; Pourcher, Valéried; Pourcher, Guillaumee; Le Grand, Rogerb; Desjardins, Delphineb; Fève, Brunoa,f; Lambotte, Olivierb,g; Capeau, Jacquelinea; Béréziat, Véroniquea,*; Lagathu, Clairea,*

doi: 10.1097/QAD.0000000000002168
BASIC SCIENCE
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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.

aSorbonne Université, INSERM UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Paris

bCEA - Université Paris Sud 11 - Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, 92265 Fontenay-aux-Roses

cAP-HP, Hôpital Tenon, Service de Chirurgie Plastique et Esthétique

dAP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Maladies Infectieuses et Tropicales, Sorbonne Université

e Institut Mutualiste Montsouris, Service de Chirurgie Digestive

fAP-HP, Hôpital Saint-Antoine, PRISIS, Service d’Endocrinologie, Diabétologie et Reproduction, Paris

gAP-HP, Groupe Hospitalier Universitaire Paris Sud, Hôpital Bicêtre, Service de Médecine Interne et Immunologie Clinique, Le Kremlin-Bicêtre, France.

Correspondence to Claire Lagathu, PhD, Sorbonne Université, INSERM UMR_S938, Centre de Recherche Saint Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), 27 rue Chaligny, 75012 Paris, France. E-mail: claire.lagathu@inserm.fr

Received 13 December, 2018

Revised 18 January, 2019

Accepted 24 January, 2019

Copyright © 2019 Wolters Kluwer Health, Inc.