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dc.contributor.authorMallon, Patrick WG
dc.contributor.authorSedwell, Rebecca
dc.contributor.authorRogers, Gary
dc.contributor.authorNolan, David
dc.contributor.authorUnemori, Patrick
dc.contributor.authorHoy, Jennifer
dc.contributor.authorSamaras, Katherine
dc.contributor.authorKelleher, Anthony
dc.contributor.authorEmery, Sean
dc.contributor.authorCooper, David A
dc.contributor.authorCarr, Andrew
dc.date.accessioned2017-05-03T15:28:34Z
dc.date.available2017-05-03T15:28:34Z
dc.date.issued2008
dc.date.modified2009-12-17T22:32:14Z
dc.identifier.issn0022-1899
dc.identifier.doi10.1086/593179
dc.identifier.urihttp://hdl.handle.net/10072/26403
dc.description.abstractBackground: Treatment of human immunodeficiency virus (HIV)-1 with thymidine-analogue nucleoside reverse-transcriptase inhibitors (tNRTIs) causes lipoatrophy, mitochondrial toxicity, and lower adipose tissue expression of peroxisome proliferator-activated receptor y (PPARy [PPARG gene]) . Rosiglitazone (RSG), a PPARy agonist, improves congenital lipoatrophy but not HIV lipoatrophy. Methods: Serial fat biopsies were taken from HIV-infected, lipoatrophic men randomized to receive RSG or placebo for 48 weeks. Adipose tissue mitochondrial and nuclear gene expression and mitochondrial DNA content were quantified by real-time polymerase chain reaction. Nonparametric analyses were applied. Results: Subjects receiving tNRTI-containing antiretroviral therapy had lower baseline mitochondrial RNA expression and DNA content. In subjects receiving tNRTIs, exposure to RSG did not affect PPARG expression at either week 2 or 48. At week 2, RSG increased PPARG expression only in subjects not treated with tNRTIs, whereas at week 48, increased PPARG expression was observed in subjects not treated with tNRTIs, regardless of RSG use. Similar findings were observed for the PPARG-responsive gene fatty acid-binding protein 4. Changes in PPARG expression were associated with increases in limb fat mass. Conclusions: These data suggest that in HIV-infected, lipoatrophic men, adipose PPARG expression and function are dependent on intact mitochondrial function. These data support a direct link between mitochondrial toxicity and adipose tissue PPARG expression and help explain the poor clinical response to RSG observed in clinical trials.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent521028 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherUniversity of Chicago Press
dc.publisher.placeUnited States
dc.publisher.urihttps://academic.oup.com/jid
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1794
dc.relation.ispartofpageto1803
dc.relation.ispartofissue12
dc.relation.ispartofjournalThe Journal of Infectious Diseases
dc.relation.ispartofvolume198
dc.rights.retentionY
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode32
dc.titleEffect of Rosiglitazone on Peroxisome Proliferator‐Activated Receptor γ Gene Expression in Human Adipose Tissue Is Limited by Antiretroviral Drug–Induced Mitochondrial Dysfunction
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2008 by University of Chicago Press. The attached file is reproduced here in accordance with the copyright policy of the publisher. First published in The Journal of Infectious Diseases with publishing partner Infectious Diseases Society of America, IDSA. Use hypertext link to access the journal's webpage.
gro.date.issued2008
gro.hasfulltextFull Text
gro.griffith.authorRogers, Gary


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