Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes
Domingo, Pere (Institut d'Investigació Biomèdica Sant Pau)
Quesada-López, Tania (Institut d'Investigació Biomèdica Sant Pau)
Villarroya, Joan (Institut de Recerca Sant Joan de Déu)
Cairó, Montserrat (Institut de Recerca Sant Joan de Déu)
Gutierrez, Mª del Mar (Institut d'Investigació Biomèdica Sant Pau)
Mateo, Maria Gracia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Mur, Isabel (Institut d'Investigació Biomèdica Sant Pau)
Corbacho, Noemí (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Domingo, Joan Carles (Universitat de Barcelona. Institut de Biomedicina)
Villarroya, Francesc (Institut de Recerca Sant Joan de Déu)
Giralt, Marta (Institut de Recerca Sant Joan de Déu)

Data:	2022
Resum:	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[sbnd]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-Ɣ 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.
Ajuts:	Instituto de Salud Carlos III PI17/00420 Instituto de Salud Carlos III PI17/00498 Instituto de Salud Carlos III PI20/00106 Instituto de Salud Carlos III PI20/00137 Agencia Estatal de Investigación IJC2020-043360-I
Nota:	Altres ajuts: European Regional Development Fund (FEDER); Gilead. European Union NextGeneration EU/PRTR.
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, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Life Sciences, Vol. 308 (january 2022) , p. 120948, ISSN 1879-0631

DOI: 10.1016/j.lfs.2022.120948
PMID: 36096241

8 p, 730.9 KB

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