{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:14:19Z","timestamp":1790874859803,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T00:00:00Z","timestamp":1654300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sidaction","award":["13006"],"award-info":[{"award-number":["13006"]}]},{"name":"Sidaction","award":["ANR-11-INBS-0008"],"award-info":[{"award-number":["ANR-11-INBS-0008"]}]},{"name":"Sidaction","award":["ANR-10-EQPX-02-01"],"award-info":[{"award-number":["ANR-10-EQPX-02-01"]}]},{"name":"Sidaction","award":["RHU-ANR-15-RHUS-0003"],"award-info":[{"award-number":["RHU-ANR-15-RHUS-0003"]}]},{"DOI":"10.13039\/501100001665","name":"Programme Investissements d\u2019Avenir","doi-asserted-by":"publisher","award":["13006"],"award-info":[{"award-number":["13006"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Programme Investissements d\u2019Avenir","doi-asserted-by":"publisher","award":["ANR-11-INBS-0008"],"award-info":[{"award-number":["ANR-11-INBS-0008"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Programme Investissements d\u2019Avenir","doi-asserted-by":"publisher","award":["ANR-10-EQPX-02-01"],"award-info":[{"award-number":["ANR-10-EQPX-02-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Programme Investissements d\u2019Avenir","doi-asserted-by":"publisher","award":["RHU-ANR-15-RHUS-0003"],"award-info":[{"award-number":["RHU-ANR-15-RHUS-0003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>For people living with HIV, treatment with integrase-strand-transfer-inhibitors (INSTIs) can promote adipose tissue (AT) gain. We previously demonstrated that INSTIs can induce hypertrophy and fibrosis in AT of macaques and humans. By promoting energy expenditure, the emergence of beige adipocytes in white AT (beiging) could play an important role by limiting excess lipid storage and associated adipocyte dysfunction. We hypothesized that INSTIs could alter AT via beiging inhibition. Fibrosis and gene expression were measured in subcutaneous (SCAT) and visceral AT (VAT) from SIV-infected, dolutegravir-treated (SIVART) macaques. Beiging capacity was assessed in human adipose stromal cells (ASCs) undergoing differentiation and being exposed to dolutegravir, bictegravir, or raltegravir. Expression of beige markers, such as positive-regulatory-domain-containing-16 (PRDM16), were lower in AT of SIVART as compared to control macaques, whereas fibrosis-related genes were higher. Dolutegravir and bictegravir inhibited beige differentiation in ASCs, as shown by lower expression of beige markers and lower cell respiration. INSTIs also induced a hypertrophic insulin-resistant state associated with a pro-fibrotic phenotype. Our results indicate that adipocyte hypertrophy induced by INSTIs is involved via hypoxia (revealed by a greater hypoxia-inducible-factor-1-alpha gene expression) in fat fibrosis, beiging inhibition, and thus (via positive feedback), probably, further hypertrophy and associated insulin resistance.<\/jats:p>","DOI":"10.3390\/cells11111841","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T09:42:32Z","timestamp":1654335752000},"page":"1841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes"],"prefix":"10.3390","volume":"11","author":[{"given":"Kenza","family":"Ngono Ayissi","sequence":"first","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gorwood","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Le Pelletier","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1146-6087","authenticated-orcid":false,"given":"Christine","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"UMR1184 Inserm, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Universit\u00e9 Paris Saclay, 92032 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Beaup\u00e8re","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Auclair","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Foresti","sequence":"additional","affiliation":[{"name":"INSERM UMR_S955, IMRB, Universit\u00e9 Paris-Est Cr\u00e9teil, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Motterlini","sequence":"additional","affiliation":[{"name":"INSERM UMR_S955, IMRB, Universit\u00e9 Paris-Est Cr\u00e9teil, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Atlan","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"Service de Chirurgie Plastique et Esth\u00e9tique, H\u00f4pital Tenon, AP-HP, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Barrail-Tran","sequence":"additional","affiliation":[{"name":"UMR1184 Inserm, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Universit\u00e9 Paris Saclay, 92032 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Le Grand","sequence":"additional","affiliation":[{"name":"UMR1184 Inserm, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Universit\u00e9 Paris Saclay, 92032 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Desjardins","sequence":"additional","affiliation":[{"name":"UMR1184 Inserm, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Universit\u00e9 Paris Saclay, 92032 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-9009","authenticated-orcid":false,"given":"Bruno","family":"F\u00e8ve","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"Service d\u2019Endocrinologie, Diab\u00e9tologie et Reproduction, H\u00f4pital Saint-Antoine, CRMR, PRISIS, AP-HP, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lambotte","sequence":"additional","affiliation":[{"name":"UMR1184 Inserm, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, CEA, Universit\u00e9 Paris Saclay, 92032 Fontenay-aux-Roses, France"},{"name":"Service de M\u00e9decine Interne et Immunologie Clinique, H\u00f4pital Bic\u00eatre, AP-HP, 94270 Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-4186","authenticated-orcid":false,"given":"Jacqueline","family":"Capeau","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9795-549X","authenticated-orcid":false,"given":"V\u00e9ronique","family":"B\u00e9r\u00e9ziat","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0700-8286","authenticated-orcid":false,"given":"Claire","family":"Lagathu","sequence":"additional","affiliation":[{"name":"Inserm UMR_S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1002\/eji.201747060","article-title":"High proportion of PD-1-expressing CD4(+) T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence","volume":"47","author":"Damouche","year":"2017","journal-title":"Eur. 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