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Conference Paper: Hypoxia inducible factor 1α plays an indispensible role in maintaining the thermogenic functions of brown adipose tissue in mice

TitleHypoxia inducible factor 1α plays an indispensible role in maintaining the thermogenic functions of brown adipose tissue in mice
Authors
KeywordsMedical sciences
Endocrinology
Issue Date2010
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
The 70th Scientific Sessions of the American Diabetes Association (ADA), Orlando, FL., 25-29 June 2010. In Diabetes, 2010, v. 59 suppl., p. A47, abstract no. 174-OR How to Cite?
AbstractHypoxia in adipose tissue has been proposed as a possible mechanism for obesity-related chronic inflammation, insulin resistance and metabolic dysfunction. Hypoxia inducible factor 1α(HIF1α), a master signal mediator of hypoxia response, is elevated in obese adipose tissue. However, the patho-physiological role of HIF1α in obesity-related pathologies remains to be determined. To address this question, we have generated a transgenic mouse model with adipose tissue-selective expression of a dominant negative version of HIF1α under the transcriptional control of the aP2 gene promoter. The transgenic mice developed more severe obesity and were more susceptible to high fat diet-induced glucose intolerance and insulin resistance compared to 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 DNA copy number and reduced expression of PGC1α and uncoupling protein-1, both of which are critically involved the biogenesis of BAT. Furthermore, impaired BAT function and reduced thermogenesis in the transgenic mice occurred prior to the development of obesity. In the transgenic mice, angiogenesis in BAT was decreased as early as four weeks after birth, but was elevated in WAT at the late stage of obesity. These findings support an indispensible role of HIF1α in maintaining the thermogenic functions of BAT, possibly through promoting angiogenesis and mitochondrial biogenesis in this tissue.
DescriptionThis journal supplement with title: Abstract Book 70th Scientific Sessions
Category: Obesity - Animal: abstract no. 174-OR
Persistent Identifierhttp://hdl.handle.net/10722/126438
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185

 

DC FieldValueLanguage
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2010-10-31T12:28:37Z-
dc.date.available2010-10-31T12:28:37Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 70th Scientific Sessions of the American Diabetes Association (ADA), Orlando, FL., 25-29 June 2010. In Diabetes, 2010, v. 59 suppl., p. A47, abstract no. 174-ORen_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/126438-
dc.descriptionThis journal supplement with title: Abstract Book 70th Scientific Sessions-
dc.descriptionCategory: Obesity - Animal: abstract no. 174-OR-
dc.description.abstractHypoxia in adipose tissue has been proposed as a possible mechanism for obesity-related chronic inflammation, insulin resistance and metabolic dysfunction. Hypoxia inducible factor 1α(HIF1α), a master signal mediator of hypoxia response, is elevated in obese adipose tissue. However, the patho-physiological role of HIF1α in obesity-related pathologies remains to be determined. To address this question, we have generated a transgenic mouse model with adipose tissue-selective expression of a dominant negative version of HIF1α under the transcriptional control of the aP2 gene promoter. The transgenic mice developed more severe obesity and were more susceptible to high fat diet-induced glucose intolerance and insulin resistance compared to 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 DNA copy number and reduced expression of PGC1α and uncoupling protein-1, both of which are critically involved the biogenesis of BAT. Furthermore, impaired BAT function and reduced thermogenesis in the transgenic mice occurred prior to the development of obesity. In the transgenic mice, angiogenesis in BAT was decreased as early as four weeks after birth, but was elevated in WAT at the late stage of obesity. These findings support an indispensible role of HIF1α in maintaining the thermogenic functions of BAT, possibly through promoting angiogenesis and mitochondrial biogenesis in this tissue.-
dc.languageengen_HK
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/-
dc.relation.ispartofDiabetesen_HK
dc.rightsThis is an author-created, uncopyedited electronic version of an article accepted for publication in TITLE [Journal URL] The American Diabetes Association (ADA), publisher of TITLE, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available online at [URL]-
dc.subjectMedical sciences-
dc.subjectEndocrinology-
dc.titleHypoxia inducible factor 1α plays an indispensible role in maintaining the thermogenic functions of brown adipose tissue in miceen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailZhang, X: xinmei_zhang@yahoo.comen_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.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.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros175938en_HK
dc.identifier.volume59en_HK
dc.identifier.issuesuppl.-
dc.identifier.spageA47-
dc.identifier.epageA47-
dc.publisher.placeUnited States-
dc.description.otherThe 70th Scientific Sessions of the American Diabetes Association (ADA), Orlando, FL., 25-29 June 2010. In Diabetes, 2010, v. 59 suppl., p. A47, abstract no. 174-OR-

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