title: Impact of elvitegravir on human adipocytes: Alterations in differentiation, gene expression and release of adipokines and cytokines.
abstract: Elvitegravir is a recently developed integrase inhibitor used for antiretroviral treatment of HIV infection. Secondary effects, including disturbances in lipid metabolism and, ultimately, in adipose tissue distribution and function, are common concerns associated with antiretroviral treatments. Here, we provide the first study of the effects of elvitegravir (in comparison with efavirenz, a non-nucleoside analog inhibitor of reverse transcriptase; and raltegravir, another integrase inhibitor) on human adipocyte differentiation, gene expression and secretion of adipokines and cytokines. Elvitegravir impaired adipogenesis and adipocyte metabolism in human SGBS adipocytes in a concentration-dependent manner (delaying acquisition of adipocyte morphology and reducing the expression of adipogenesis marker genes such as PPARγ, glucose transporter GLUT4, lipoprotein lipase, and the adipokines adiponectin and leptin). Compared with efavirenz, the effects of elvitegravir were similar but tended to occur at higher concentrations than those elicited by efavirenz, or were somewhat less intense than those caused by efavirenz at similar concentration. Elvitegravir tended to cause a more moderate induction of pro-inflammatory cytokines than efavirenz. Efavirenz induced a marked concentration-dependent increase in interleukin-8 expression and release whereas elvitregravir had little effect. Raltegravir had totally neutral actions of adipogenesis, adipocyte metabolism-related gene expression and release of adipokines and cytokines. In conclusion, elvitegravir alters adipocyte differentiation and function and promotes induction of pro-inflammatory cytokines similarly to efavirenz, but several effects were less intense. Further assessment of lipid metabolism and adipose tissue function in patients administered elvitegravir-based regimes is advisable considering that totally neutral effects of elvitegravir on lipid homeostasis cannot be anticipated from the current study in vitro.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina (IBUB), University of Barcelona, CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Moure
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona and Red de Investigación en SIDA (RIS), Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina (IBUB), University of Barcelona, CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Gallego-Escuredo
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina (IBUB), University of Barcelona, CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain; Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona and Red de Investigación en SIDA (RIS), Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Villarroya
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona and Red de Investigación en SIDA (RIS), Barcelona, Spain.
authors.forename: Maria Del Mar
authors.initials: Mdel M
authors.lastname: Gutierrez
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona and Red de Investigación en SIDA (RIS), Barcelona, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Mateo
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina (IBUB), University of Barcelona, CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
authors.forename: Joan C
authors.initials: JC
authors.lastname: Domingo
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina (IBUB), University of Barcelona, CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Giralt
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina (IBUB), University of Barcelona, CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Spain. Electronic address: fvillarroya@ub.edu.
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D054392:Adipokines / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D054392:Adipokines; D016207:Cytokines; D019428:HIV Integrase Inhibitors; D018836:Inflammation Mediators; D015363:Quinolones; C509700:elvitegravir
keywords: Adipocyte; Adipokine; Cytokine; Efavirenz; Elvitegravir; Lipodystrophy