Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-13
pubmed:abstractText
The non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz are drugs of choice for initial antiretroviral treatment for HIV-1 infection. Although NNRTIs have not traditionally been associated with the appearance of adipose alterations, recent data suggest that efavirenz may contribute to adipose tissue alterations in antiretroviral-treated patients, consistent with its ability to impair differentiation of adipocytes in cell cultures. No such effects have been reported for nevirapine, the other most commonly used NNRTI. In this study, we determined the effects of nevirapine on differentiation, gene expression and release of regulatory proteins (adipokines and cytokines) in differentiating human adipocytes, and compared them with those of efavirenz. Efavirenz caused a dose-dependent repression of adipocyte differentiation that was associated with down-regulation of the master adipogenesis regulator genes SREBP-1, PPAR? and C/EBP?, and their target genes encoding lipoprotein lipase, leptin and adiponectin, which are key proteins in adipocyte function. In contrast, nevirapine does not affect adipogenesis and causes a modest but significant coordinate increase in the expression of SREBP-1, PPAR? and C/EBP? and their target genes only at a concentration of 20 ?M. Whereas efavirenz caused a significant increase in the release of pro-inflammatory cytokines (interleukin [IL]-8, IL-6, monocyte chemoattractant protein-1), plasminogen activator inhibitor type-1 and hepatocyte growth factor (HGF), nevirapine either had no effect on these factors or decreased their release (IL-6 and HGF). Nevirapine significantly increased adiponectin release, whereas efavirenz strongly repressed it. Moreover, nevirapine inhibited preadipocyte endogenous reverse transcriptase activity, whereas efavirenz did not alter it. It is concluded that, in contrast with the profound anti-adipogenic and pro-inflammatory response elicited by efavirenz, nevirapine does not impair adipogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adipokines, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Retroviral Agents, http://linkedlifedata.com/resource/pubmed/chemical/Benzoxazines, http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-alpha, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Lactic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Nevirapine, http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma, http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1, http://linkedlifedata.com/resource/pubmed/chemical/RNA-Directed DNA Polymerase, http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding..., http://linkedlifedata.com/resource/pubmed/chemical/efavirenz
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1872-9096
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
112-9
pubmed:meshHeading
pubmed-meshheading:21619898-Adipocytes, pubmed-meshheading:21619898-Adipogenesis, pubmed-meshheading:21619898-Adipokines, pubmed-meshheading:21619898-Anti-Retroviral Agents, pubmed-meshheading:21619898-Benzoxazines, pubmed-meshheading:21619898-CCAAT-Enhancer-Binding Protein-alpha, pubmed-meshheading:21619898-Cell Survival, pubmed-meshheading:21619898-Cells, Cultured, pubmed-meshheading:21619898-Cytokines, pubmed-meshheading:21619898-Down-Regulation, pubmed-meshheading:21619898-Gene Expression, pubmed-meshheading:21619898-Hepatocyte Growth Factor, pubmed-meshheading:21619898-Humans, pubmed-meshheading:21619898-Lactic Acid, pubmed-meshheading:21619898-Microbial Sensitivity Tests, pubmed-meshheading:21619898-Nevirapine, pubmed-meshheading:21619898-PPAR gamma, pubmed-meshheading:21619898-Plasminogen Activator Inhibitor 1, pubmed-meshheading:21619898-RNA-Directed DNA Polymerase, pubmed-meshheading:21619898-Sterol Regulatory Element Binding Protein 1
pubmed:year
2011
pubmed:articleTitle
Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines.
pubmed:affiliation
Department of Biochemistry and Molecular Biology and Institut de Biomedicina (IBUB), University of Barcelona and CIBER Fisiopatología de la Obesidad y Nutrición, Spain.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't