2. Academic Validation
  3. Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function

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

  • Biochem Pharmacol. 2023 Dec 26:116010. doi: 10.1016/j.bcp.2023.116010.
T Quesada-López 1,  R Cereijo 2,  A Blasco-Roset 2,  A Mestres-Arenas 2,  P Prieto 3,  J C Domingo 4,  F Villarroya 5,  P Domingo 6,  M Giralt 7
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain; Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain; Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
  • 2 Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
  • 3 Department of Infectious Diseases, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain; Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain.
  • 4 Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
  • 5 Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Catalonia, Spain.
  • 6 Department of Infectious Diseases, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain; Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain. Electronic address: pdomingo@santpau.cat.
  • 7 Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Catalonia, Spain. Electronic address: mgiralt@ub.edu.
PMID: 38154544 DOI: 10.1016/j.bcp.2023.116010
Abstract

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). Selected gene markers expression was determined by qPCR, the release of adipokines and inflammatory cytokines to the culture media were 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 increase this effect. Thus, DTG repressed the expression of Adiponectin and the release of Adiponectin and Leptin in differentiating adipocytes, and these effects were decreased 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.

Keywords

Adipocyte; Adipokine; Adiposity; Dolutegravir; Tenofovir alafenamide; Tenofovir disoproxil fumarate.

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