Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
Por:
Quesada-López, T, Cereijo, R, Blasco-Roset, A, Mestres-Arenas, A, Prieto, P, Domingo, JC, Villarroya, F, Domingo, P, Giralt, M
Publicada:
1 feb 2024
Ahead of Print:
1 ene 2024
Resumen:
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.
Filiaciones:
Quesada-López, T:
Hosp Santa Creu i Sant Pau, Dept Infect Dis, Barcelona, Spain
Inst Recerca lHosp Santa Creu i Santa Pau, Barcelona, Spain
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr CIBEROBN, Madrid, Spain
Cereijo, R:
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr CIBEROBN, Madrid, Spain
Blasco-Roset, A:
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr CIBEROBN, Madrid, Spain
Mestres-Arenas, A:
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr CIBEROBN, Madrid, Spain
Prieto, P:
Hosp Santa Creu i Sant Pau, Dept Infect Dis, Barcelona, Spain
Inst Recerca lHosp Santa Creu i Santa Pau, Barcelona, Spain
Domingo, JC:
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona, Spain
Villarroya, F:
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr CIBEROBN, Madrid, Spain
Domingo, P:
Hosp Santa Creu i Sant Pau, Dept Infect Dis, Barcelona, Spain
Inst Recerca lHosp Santa Creu i Santa Pau, Barcelona, Spain
Inst Recerca Sant Joan Deu IRSJD, Esplugas de Llobregat, Spain
Giralt, M:
Univ Barcelona, Dept Bioquim & Biomed Mol, Fac Biol, Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr CIBEROBN, Madrid, Spain
Inst Recerca Sant Joan Deu IRSJD, Esplugas de Llobregat, Spain
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