| First Author | Lee KY | Year | 2011 |
| Journal | Cell Metab | Volume | 14 |
| Issue | 4 | Pages | 491-503 |
| PubMed ID | 21982709 | Mgi Jnum | J:177646 |
| Mgi Id | MGI:5295786 | Doi | 10.1016/j.cmet.2011.08.006 |
| Citation | Lee KY, et al. (2011) The differential role of Hif1beta/Arnt and the hypoxic response in adipose function, fibrosis, and inflammation. Cell Metab 14(4):491-503 |
| abstractText | In obesity, adipocytes distant from vasculature become hypoxic and dysfunctional. This hypoxic response is mediated by hypoxia-inducible factors (Hif1alpha, Hif2alpha, and Hif3alpha) and their obligate partner, Hif1beta (Arnt). We show that mice lacking Hif1beta in fat (FH1betaKO) are lean, exhibit reduced adipocyte size, and are protected from age- and diet-induced glucose intolerance. There is also reduced Vegf and vascular permeability in FH1betaKO fat, but diet-induced inflammation and fibrosis is unchanged. Adipocytes from FH1betaKO mice have reduced glucose uptake due to decreased Glut1 and Glut4, which is mirrored in 3T3-L1 adipocytes with Hif1beta knockdown. Hif1beta knockdown cells also fail to respond appropriately to hypoxia with reduced cellular respiration and reduced mitochondrial gene expression. Some, but not all, of these effects are reproduced by Hif1alpha knockdown. Thus, Hif1beta/Arnt regulates glucose uptake, mitochondrial gene expression, and vascular permeability to control adipose mass and function, providing a target for obesity therapy. |
