Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
Quesada-López, Tania (Institut de Recerca Sant Pau)
Blasco-Roset, Albert (Universitat de Barcelona)
Mestres-Arenas, Alberto (Universitat de Barcelona)
Prieto, P. (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Villarroya, Francesc (Institut de Recerca Sant Joan de Déu)
Domingo Pedrol, Pedro (Institut de Recerca Sant Pau)
Girlat, Marta (Institut de Recerca Sant Joan de Déu)
Cereijo, R. (Instituto de Salud Carlos III)
Domingo, J.C. (Universitat de Barcelona)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI20/00106 Instituto de Salud Carlos III PI20/00137 Ministerio de Ciencia e Innovación IJC2020-043360-I
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adipocyte ; Adipokine ; Adiposity ; Dolutegravir ; Tenofovir alafenamide ; Tenofovir disoproxil fumarate
Publicat a:	Biochemical pharmacology, Vol. 220 (February 2024) , art. 116010, ISSN 1873-2968

DOI: 10.1016/j.bcp.2023.116010
PMID: 38154544

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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