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Adipocyte-Specific Hypoxia-Inducible Factor 2alpha Deficiency Exacerbates Obesity-Induced Brown Adipose Tissue Dysfunction and Metabolic Dysregulation.

Authors: Garcia-Martin, R  Alexaki, VI  Qin, N  Rubin de Celis, MF  Economopoulou, M  Ziogas, A  Gercken, B  Kotlabova, K  Phieler, J  Ehrhart-Bornstein, M  Bornstein, SR  Eisenhofer, G  Breier, G  Bluher, M  Hampe, J  El-Armouche, A  Chatzigeorgiou, A  Chung, KJ  Chavakis, T 
Citation: Garcia-Martin R, etal., Mol Cell Biol. 2015 Nov 16;36(3):376-93. doi: 10.1128/MCB.00430-15.
Pubmed: (View Article at PubMed) PMID:26572826
DOI: Full-text: DOI:10.1128/MCB.00430-15

Angiogenesis is a central regulator for white (WAT) and brown (BAT) adipose tissue adaptation in the course of obesity. Here we show that deletion of hypoxia-inducible factor 2alpha (HIF2alpha) in adipocytes (by using Fabp4-Cre transgenic mice) but not in myeloid or endothelial cells negatively impacted WAT angiogenesis and promoted WAT inflammation, WAT dysfunction, hepatosteatosis, and systemic insulin resistance in obesity. Importantly, adipocyte HIF2alpha regulated vascular endothelial growth factor (VEGF) expression and angiogenesis of obese BAT as well as its thermogenic function. Consistently, obese adipocyte-specific HIF2alpha-deficient mice displayed BAT dysregulation, associated with reduced levels of uncoupling protein 1 (UCP1) and a dysfunctional thermogenic response to cold exposure. VEGF administration reversed WAT and BAT inflammation and BAT dysfunction in adipocyte HIF2alpha-deficient mice. Together, our findings show that adipocyte HIF2alpha is protective against maladaptation to obesity and metabolic dysregulation by promoting angiogenesis in both WAT and BAT and by counteracting obesity-mediated BAT dysfunction.

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RGD Object Information
RGD ID: 11251638
Created: 2016-06-15
Species: All species
Last Modified: 2016-06-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.