Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1 alpha

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSHIN, Mi-Kyung
dc.contributor.authorDRAGER, Luciano F.
dc.contributor.authorYAO, Qiaoling
dc.contributor.authorBEVANS-FONTI, Shannon
dc.contributor.authorYOO, Doo-Young
dc.contributor.authorJUN, Jonathan C.
dc.contributor.authorAJA, Susan
dc.contributor.authorBHANOT, Sanjay
dc.contributor.authorPOLOTSKY, Vsevolod Y.
dc.date.accessioned2013-07-30T17:52:30Z
dc.date.available2013-07-30T17:52:30Z
dc.date.issued2012
dc.description.abstractObesity is associated with tissue hypoxia and the up-regulation of hypoxia inducible factor 1 alpha (HIF-1 alpha). Prior studies in transgenic mice have shown that HIF-1 alpha plays a role in the metabolic dysfunction associated with obesity. Therefore, we hypothesized that, after the development of diet-induced obesity (DIO), metabolic function could be improved by administration of HIF-1 alpha antisense oligonucleotides (ASO). DIO mice were treated with HIF-1 alpha ASO or with control ASO for 8 weeks and compared with an untreated group. We found that HIF-1 alpha ASO markedly suppressed Hif-1 alpha gene expression in adipose tissue and the liver. HIF-1 alpha ASO administration induced weight loss. Final body weight was 41.6 +/- 1.4 g in the HIF-1 alpha ASO group vs 46.7 +/- 0.9 g in the control ASO group and 47.9 +/- 0.8 g in untreated mice (p<0.001). HIF-1 alpha ASO increased energy expenditure (13.3 +/- 0.6 vs 12 +/- 0.1 and 11.9 +/- 0.4 kcal/kg/hr, respectively, p<0.001) and decreased the respiratory exchange ratio (0.71 +/- 0.01 vs 0.75 +/- 0.01 and 0.76 +/- 0.01, respectively, p<0.001), which suggested switching metabolism to fat oxidation. In contrast, HIF-1a ASO had no effect on food intake or activity. HIF-1 alpha ASO treatment decreased fasting blood glucose (195.5 +/- 8.4 mg/dl vs 239 +/- 7.8 mg/dl in the control ASO group and 222 +/- 8.2 mg/dl in untreated mice, p<0.01), plasma insulin, hepatic glucose output, and liver fat content. These findings demonstrate that the metabolic consequences of DIO are attenuated by HIF-1 alpha ASO treatment.
dc.description.indexMEDLINE
dc.description.sponsorshipNational Institutes of Health (NIH) [R01 HL080105, P50 HL084945]
dc.description.sponsorshipAmerican Heart Association [10GRNT3360001]
dc.identifier.citationPLOS ONE, v.7, n.10, article ID e46562, 10p, 2012
dc.identifier.doi10.1371/journal.pone.0046562
dc.identifier.issn1932-6203
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1467
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.ispartofPlos One
dc.rightsopenAccess
dc.rights.holderCopyright PUBLIC LIBRARY SCIENCE
dc.subject.otherinducible factor 1-alpha
dc.subject.otherbrown adipose-tissue
dc.subject.otherchronic intermittent hypoxia
dc.subject.otherinsulin-resistance
dc.subject.otherlipid-metabolism
dc.subject.otherobese mice
dc.subject.otherenergy-expenditure
dc.subject.otherlean mice
dc.subject.otherglucose
dc.subject.otheroxygen
dc.subject.wosMultidisciplinary Sciences
dc.titleMetabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1 alpha
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalSHIN, Mi-Kyung:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA
hcfmusp.author.externalYAO, Qiaoling:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA
hcfmusp.author.externalBEVANS-FONTI, Shannon:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA
hcfmusp.author.externalYOO, Doo-Young:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA
hcfmusp.author.externalJUN, Jonathan C.:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA
hcfmusp.author.externalAJA, Susan:Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
hcfmusp.author.externalBHANOT, Sanjay:Isis Pharmaceut Inc, Carlsbad, CA USA
hcfmusp.author.externalPOLOTSKY, Vsevolod Y.:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA
hcfmusp.citation.scopus55
hcfmusp.contributor.author-fmusphcLUCIANO FERREIRA DRAGER
hcfmusp.description.articlenumbere46562
hcfmusp.description.issue10
hcfmusp.description.volume7
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed23049707
hcfmusp.origem.scopus2-s2.0-84867030992
hcfmusp.origem.wosWOS:000309388500034
hcfmusp.publisher.citySAN FRANCISCO
hcfmusp.publisher.countryUSA
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hcfmusp.remissive.sponsorshipNIH
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