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2024-02-01

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cc-by-nc (c) Quesada López, Tania Paloma et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/220810

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

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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 Simpson-Golabi-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.

Descripció

Matèries

Teixit adipós, Trastorns del metabolisme, Inhibidors de la integrasa, Antiretrovirals

Matèries (anglès)

Adipose tissues, Disorders of metabolism, Integrase inhibitors, Antiretroviral agents

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

QUESADA LÓPEZ, Tania paloma, CEREIJO TÉLLEZ, Rubén, BLASCO ROSET, Albert, MESTRES ARENAS, Alberto, PRIETO, Patricia, DOMINGO I PEDROL, Joan carles, VILLARROYA I GOMBAU, Francesc, DOMINGO, Pere (domingo pedrol), GIRALT I OMS, Marta. Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function. _Biochemical Pharmacology_. 2024. Vol. 220, núm. 1-11. [consulta: 24 de novembre de 2025]. ISSN: 0006-2952. [Disponible a: https://hdl.handle.net/2445/220810]

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