{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:14:13Z","timestamp":1790874853797,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les h\u00e9patites virales","doi-asserted-by":"publisher","award":["N17020DR"],"award-info":[{"award-number":["N17020DR"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les h\u00e9patites virales","doi-asserted-by":"publisher","award":["ECTZ103291"],"award-info":[{"award-number":["ECTZ103291"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les h\u00e9patites virales","doi-asserted-by":"publisher","award":["10744"],"award-info":[{"award-number":["10744"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les h\u00e9patites virales","doi-asserted-by":"publisher","award":["12152"],"award-info":[{"award-number":["12152"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programme Investissements d\u2019Avenir","award":["ANR-11-INBS-0008"],"award-info":[{"award-number":["ANR-11-INBS-0008"]}]},{"name":"Programme Investissements d\u2019Avenir","award":["ANR-10-EQPX-02\u201301"],"award-info":[{"award-number":["ANR-10-EQPX-02\u201301"]}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["EQU201903007868"],"award-info":[{"award-number":["EQU201903007868"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although some integrase strand transfer inhibitors (INSTIs) promote peripheral and central adipose tissue\/weight gain in people with human immunodeficiency virus (PHIV), the underlying mechanism has not been identified. Here, we used human and simian models to assess the impact of INSTIs on adipose tissue phenotype and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adipocyte size and fibrosis were determined in biopsies of subcutaneous and visceral adipose tissue (SCAT and VAT, respectively) from 14 noninfected macaques and 19 PHIV treated or not treated with an INSTI. Fibrosis, adipogenesis, oxidative stress, mitochondrial function, and insulin sensitivity were assessed in human proliferating or adipocyte-differentiated adipose stem cells after long-term exposure to dolutegravir or raltegravir.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed elevated fibrosis, adipocyte size, and adipogenic marker expression in SCAT and VAT from INSTI-treated noninfected macaques. Adiponectin expression was low in SCAT. Accordingly, SCAT and VAT samples from INSTI-exposed patients displayed higher levels of fibrosis than those from nonexposed patients. In vitro, dolutegravir and, to a lesser extent, raltegravir were associated with greater extracellular matrix production and lipid accumulation in adipose stem cells and\/or adipocytes as observed in vivo. Despite the INSTIs\u2019 proadipogenic and prolipogenic effects, these drugs promoted oxidative stress, mitochondrial dysfunction, and insulin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dolutegravir and raltegravir can directly impact adipocytes and adipose tissue. These INSTIs induced adipogenesis, lipogenesis, oxidative stress, fibrosis, and insulin resistance. The present study is the first to shed light on the fat modifications observed in INSTI-treated PHIV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaa259","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T16:22:26Z","timestamp":1583770946000},"page":"e549-e560","source":"Crossref","is-referenced-by-count":149,"title":["The Integrase Inhibitors Dolutegravir and Raltegravir Exert Proadipogenic and Profibrotic Effects and Induce Insulin Resistance in Human\/Simian Adipose Tissue and Human Adipocytes"],"prefix":"10.1093","volume":"71","author":[{"given":"Jennifer","family":"Gorwood","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm Unit\u00e9 Mixte de Recherche S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris Sud 11, Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Pourcher","sequence":"additional","affiliation":[{"name":"Assistance publique\u2013H\u00f4pitaux de Paris, Sorbonne Universit\u00e9, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Service de maladies infectieuses et tropicales, Paris, France"},{"name":"Sorbonne Universit\u00e9-Inserm, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Pourcher","sequence":"additional","affiliation":[{"name":"Obesity Center, Institut Mutualiste Montsouris, Paris Descartes University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Charlotte","sequence":"additional","affiliation":[{"name":"Assistance publique\u2013H\u00f4pitaux de Paris, Sorbonne Universit\u00e9, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Service d\u2019Anatomie Pathologique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Mantecon","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm Unit\u00e9 Mixte de Recherche S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Rose","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm Unit\u00e9 Mixte de Recherche S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Morichon","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm Unit\u00e9 Mixte de Recherche S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Atlan","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm Unit\u00e9 Mixte de Recherche S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition, Paris, France"},{"name":"Assistance publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Tenon, Service de Chirurgie Plastique et Esth\u00e9tique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Le Grand","sequence":"additional","affiliation":[{"name":"Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris Sud 11, Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Desjardins","sequence":"additional","affiliation":[{"name":"Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris Sud 11, Inserm U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Infectious Disease Models and Innovative Therapies Department, Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Katlama","sequence":"additional","affiliation":[{"name":"Assistance publique\u2013H\u00f4pitaux de Paris, Sorbonne Universit\u00e9, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Service de maladies infectieuses et tropicales, Paris, France"},{"name":"Sorbonne Universit\u00e9-Inserm, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"F\u00e8ve","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm Unit\u00e9 Mixte de Recherche S938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition, Paris, France"},{"name":"Assistance publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Saint-Antoine, Pathologies de la R\u00e9sistance \u00e0 l\u2019Insuline et de l\u2019Insulino-Sensibilit\u00e9, Service 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