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Article: Adipose tissue-specific inhibition of hypoxia-inducible factor 1α induces obesity and glucose intolerance by impeding energy expenditure in mice

TitleAdipose tissue-specific inhibition of hypoxia-inducible factor 1α induces obesity and glucose intolerance by impeding energy expenditure in mice
Authors
Issue Date2010
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2010, v. 285 n. 43, p. 32869-32877 How to Cite?
AbstractHypoxia in adipose tissue has been postulated as a possible contributor to obesity-related chronic inflammation, insulin resistance, and metabolic dysfunction. HIF1α (hypoxia-inducible factor 1α), a master signal mediator of hypoxia response, is elevated in obese adipose tissue. However, the role of HIF1α in obesity-related pathologies remains to be determined. Here we show that transgenic mice with adipose tissue-selective expression of a dominant negative version of HIF1α developed more severe obesity and were more susceptible to high fat diet-induced glucose intolerance and insulin resistance compared with their wild type littermates. Obesity in the transgenic mice was attributed to impaired energy expenditure and reduced thermogenesis. Histological examination of interscapular brown adipose tissue (BAT) in the transgenic mice demonstrated a markedly increased size of lipid droplets and decreased mitochondrial density in adipocytes, a phenotype similar to that in white adipose tissue. These changes in BAT of the transgenic mice were accompanied by decreased mitochondrial biogenesis and reduced expression of key thermogenic genes. In the transgenic mice, angiogenesis in BAT was decreased but was little affected in white adipose tissue. These findings support an indispensable role of HIF1α in maintaining the thermogenic functions of BAT, possibly through promoting angiogenesis and mitochondrial biogenesis in this tissue. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/142384
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 7645/06M
Collaborative Research FundHKU 2/07C
Natural Science Foundation of China30600300
University of Hong Kong
Funding Information:

This work was supported by Research Grants Council of Hong Kong General Research Fund Grant HKU 7645/06M and Collaborative Research Fund Grant HKU 2/07C, Natural Science Foundation of China Grant 30600300, and an Outstanding Young Researcher Award from the University of Hong Kong (to A. X.).

References
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DC FieldValueLanguage
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorYe, Hen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorZhou, Men_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2011-10-28T02:44:46Z-
dc.date.available2011-10-28T02:44:46Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2010, v. 285 n. 43, p. 32869-32877en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142384-
dc.description.abstractHypoxia in adipose tissue has been postulated as a possible contributor to obesity-related chronic inflammation, insulin resistance, and metabolic dysfunction. HIF1α (hypoxia-inducible factor 1α), a master signal mediator of hypoxia response, is elevated in obese adipose tissue. However, the role of HIF1α in obesity-related pathologies remains to be determined. Here we show that transgenic mice with adipose tissue-selective expression of a dominant negative version of HIF1α developed more severe obesity and were more susceptible to high fat diet-induced glucose intolerance and insulin resistance compared with their wild type littermates. Obesity in the transgenic mice was attributed to impaired energy expenditure and reduced thermogenesis. Histological examination of interscapular brown adipose tissue (BAT) in the transgenic mice demonstrated a markedly increased size of lipid droplets and decreased mitochondrial density in adipocytes, a phenotype similar to that in white adipose tissue. These changes in BAT of the transgenic mice were accompanied by decreased mitochondrial biogenesis and reduced expression of key thermogenic genes. In the transgenic mice, angiogenesis in BAT was decreased but was little affected in white adipose tissue. These findings support an indispensable role of HIF1α in maintaining the thermogenic functions of BAT, possibly through promoting angiogenesis and mitochondrial biogenesis in this tissue. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.subject.meshAdipose Tissue, Brown - metabolism-
dc.subject.meshEnergy Metabolism-
dc.subject.meshGlucose Intolerance - genetics - metabolism-
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit - genetics - metabolism-
dc.subject.meshObesity - genetics - metabolism-
dc.titleAdipose tissue-specific inhibition of hypoxia-inducible factor 1α induces obesity and glucose intolerance by impeding energy expenditure in miceen_HK
dc.typeArticleen_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M110.135509en_HK
dc.identifier.pmid20716529-
dc.identifier.pmcidPMC2963410-
dc.identifier.scopuseid_2-s2.0-77958508121en_HK
dc.identifier.hkuros184656en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77958508121&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume285en_HK
dc.identifier.issue43en_HK
dc.identifier.spage32869en_HK
dc.identifier.epage32877en_HK
dc.identifier.isiWOS:000283048200024-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectnull-
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.identifier.scopusauthoridZhang, X=37021957200en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridYe, H=7201887749en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridZhou, M=14629760500en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK

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