Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes
Por:
Domingo, P, Quesada-Lopez, T, Villarroya, J, Cairo, M, Gutierrez, MD, Mateo, MG, Mur, I, Corbacho, N, Domingo, JC, Villarroya, F, Giralt, M
Publicada:
1 nov 2022
Resumen:
Aims: To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells.
Main methods: Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (C-C motif) ligand-2 using Multiplex assays.
Key findings: Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-gamma and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir.
Significance: The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH.
Filiaciones:
Domingo, P:
Hosp Santa Creu & Sant Pau, Dept Infect Dis, Barcelona, Catalonia, Spain
Inst Recerca Hosp Santa Creu & St Pau, Barcelona, Catalonia, Spain
Quesada-Lopez, T:
Hosp Santa Creu & Sant Pau, Dept Infect Dis, Barcelona, Catalonia, Spain
Inst Recerca Hosp Santa Creu & St Pau, Barcelona, Catalonia, Spain
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Diagonal 643, Barcelona 08028, Catalonia, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Catalonia, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain
Inst Recerca St Joan de Deu IRSJD, Esplugas de Llobregat, Catalonia, Spain
Villarroya, J:
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Diagonal 643, Barcelona 08028, Catalonia, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Catalonia, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain
Inst Recerca St Joan de Deu IRSJD, Esplugas de Llobregat, Catalonia, Spain
Cairo, M:
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Diagonal 643, Barcelona 08028, Catalonia, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Catalonia, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain
Inst Recerca St Joan de Deu IRSJD, Esplugas de Llobregat, Catalonia, Spain
Gutierrez, MD:
Hosp Santa Creu & Sant Pau, Dept Infect Dis, Barcelona, Catalonia, Spain
Inst Recerca Hosp Santa Creu & St Pau, Barcelona, Catalonia, Spain
Mateo, MG:
Hosp Santa Creu & Sant Pau, Dept Infect Dis, Barcelona, Catalonia, Spain
Inst Recerca Hosp Santa Creu & St Pau, Barcelona, Catalonia, Spain
Mur, I:
Hosp Santa Creu & Sant Pau, Dept Infect Dis, Barcelona, Catalonia, Spain
Inst Recerca Hosp Santa Creu & St Pau, Barcelona, Catalonia, Spain
Corbacho, N:
Hosp Santa Creu & Sant Pau, Dept Infect Dis, Barcelona, Catalonia, Spain
Inst Recerca Hosp Santa Creu & St Pau, Barcelona, Catalonia, Spain
Domingo, JC:
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Diagonal 643, Barcelona 08028, Catalonia, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Catalonia, Spain
Villarroya, F:
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Diagonal 643, Barcelona 08028, Catalonia, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Catalonia, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain
Inst Recerca St Joan de Deu IRSJD, Esplugas de Llobregat, Catalonia, Spain
Giralt, M:
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Diagonal 643, Barcelona 08028, Catalonia, Spain
Univ Barcelona, Inst Biomed IBUB, Barcelona, Catalonia, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Madrid, Spain
Inst Recerca St Joan de Deu IRSJD, Esplugas de Llobregat, Catalonia, Spain
hybrid, All Open Access; Hybrid Gold
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