Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function

Combined antiretroviral therapy (cART) has been associated with increased body weight accompanied by metabolic alterations in people living with human immunodeficiency virus (PLWH). To gain insight into the combined effects of cART components on adipocyte dysfunction, we assessed whether and how tre...

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Autores: Quesada-López, T, Cereijo, R, Blasco-Roset, A, Mestres-Arenas, A, Prieto, P, Domingo, JC, Villarroya, F, Domingo, P, Giralt, M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p17794
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17794
https://ddd.uab.cat/record/298680
Access Level:acceso abierto
Palabra clave:Adipocyte
Adiposity
Dolutegravir
Tenofovir alafenamide
Tenofovir disoproxil fumarate
Adipokine
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spelling Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte functionQuesada-López, TCereijo, RBlasco-Roset, AMestres-Arenas, APrieto, PDomingo, JCVillarroya, FDomingo, PGiralt, MAdipocyteAdiposityDolutegravirTenofovir alafenamideTenofovir disoproxil fumarateAdipokineCombined antiretroviral therapy (cART) has been associated with increased body weight accompanied by metabolic alterations in people living with human immunodeficiency virus (PLWH). To gain insight into the combined effects of cART components on adipocyte dysfunction, we assessed whether and how treatment of human adipocytes with dolutegravir (DTG) and the nucleotide-analog reverse-transcriptase inhibitors (NRTIs), tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), alone and in combination, altered biological processes related to adipose tissue dysfunction. DTG, TAF, and TDF were applied to human SimpsonGolabi-Behmel syndrome (SGBS) adipose cells during differentiation (day 10) and ensuing differentiation (day 14). Expression of selected marker genes was determined by qPCR, the release of adipokines and inflammatory cytokines to the culture media was assessed, and cell respiration was measured. Adipogenesis was not altered by the combined treatment of human adipocytes. However, DTG at the highest dose repressed adipogenesis marker genes expression, and TAF and TDF appeared to mitigate this effect. DTG repressed the expression of adiponectin and the release of adiponectin and leptin in differentiating adipocytes, and these effects were mantained in combination with TAF and TDF. DTG plus TAF or TDF on human adipocytes enhanced inflammation and stress and increased the release of proinflammatory cytokines to the culture media. Together, our results show that combined therapy with these drugs can alter inflammation, cellular stress, and fibrosis in human adipocytes. These findings may improve our understanding and management of the effects of cART on body adiposity and metabolic dysregulation in PLWH.PERGAMON-ELSEVIER SCIENCE LTD2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17794https://ddd.uab.cat/record/298680BIOCHEMICAL PHARMACOLOGYISSN: 00062952ISSNe: 18732968reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p177942026-06-14T12:41:47Z
dc.title.none.fl_str_mv Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
title Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
spellingShingle Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
Quesada-López, T
Adipocyte
Adiposity
Dolutegravir
Tenofovir alafenamide
Tenofovir disoproxil fumarate
Adipokine
title_short Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
title_full Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
title_fullStr Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
title_full_unstemmed Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
title_sort Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
dc.creator.none.fl_str_mv Quesada-López, T
Cereijo, R
Blasco-Roset, A
Mestres-Arenas, A
Prieto, P
Domingo, JC
Villarroya, F
Domingo, P
Giralt, M
author Quesada-López, T
author_facet Quesada-López, T
Cereijo, R
Blasco-Roset, A
Mestres-Arenas, A
Prieto, P
Domingo, JC
Villarroya, F
Domingo, P
Giralt, M
author_role author
author2 Cereijo, R
Blasco-Roset, A
Mestres-Arenas, A
Prieto, P
Domingo, JC
Villarroya, F
Domingo, P
Giralt, M
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adipocyte
Adiposity
Dolutegravir
Tenofovir alafenamide
Tenofovir disoproxil fumarate
Adipokine
topic Adipocyte
Adiposity
Dolutegravir
Tenofovir alafenamide
Tenofovir disoproxil fumarate
Adipokine
description Combined antiretroviral therapy (cART) has been associated with increased body weight accompanied by metabolic alterations in people living with human immunodeficiency virus (PLWH). To gain insight into the combined effects of cART components on adipocyte dysfunction, we assessed whether and how treatment of human adipocytes with dolutegravir (DTG) and the nucleotide-analog reverse-transcriptase inhibitors (NRTIs), tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), alone and in combination, altered biological processes related to adipose tissue dysfunction. DTG, TAF, and TDF were applied to human SimpsonGolabi-Behmel syndrome (SGBS) adipose cells during differentiation (day 10) and ensuing differentiation (day 14). Expression of selected marker genes was determined by qPCR, the release of adipokines and inflammatory cytokines to the culture media was assessed, and cell respiration was measured. Adipogenesis was not altered by the combined treatment of human adipocytes. However, DTG at the highest dose repressed adipogenesis marker genes expression, and TAF and TDF appeared to mitigate this effect. DTG repressed the expression of adiponectin and the release of adiponectin and leptin in differentiating adipocytes, and these effects were mantained in combination with TAF and TDF. DTG plus TAF or TDF on human adipocytes enhanced inflammation and stress and increased the release of proinflammatory cytokines to the culture media. Together, our results show that combined therapy with these drugs can alter inflammation, cellular stress, and fibrosis in human adipocytes. These findings may improve our understanding and management of the effects of cART on body adiposity and metabolic dysregulation in PLWH.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17794
https://ddd.uab.cat/record/298680
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17794
https://ddd.uab.cat/record/298680
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv PERGAMON-ELSEVIER SCIENCE LTD
publisher.none.fl_str_mv PERGAMON-ELSEVIER SCIENCE LTD
dc.source.none.fl_str_mv BIOCHEMICAL PHARMACOLOGY
ISSN: 00062952
ISSNe: 18732968
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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