| First Author | He Q | Year | 2011 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 300 |
| Issue | 5 | Pages | E877-85 |
| PubMed ID | 21343542 | Mgi Jnum | J:172307 |
| Mgi Id | MGI:5006899 | Doi | 10.1152/ajpendo.00626.2010 |
| Citation | He Q, et al. (2011) Regulation of HIF-1{alpha} activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia. Am J Physiol Endocrinol Metab 300(5):E877-85 |
| abstractText | The transcription factor HIF-1alpha activity is increased in adipose tissue to contribute to chronic inflammation in obesity. However, its upstream and downstream events remain to be characterized in adipose tissue in obesity. We addressed this issue by investigating adipocyte HIF-1alpha activity in response to obesity-associated factors, such as adipogenesis, insulin, and hypoxia. In adipose tissue, both HIF-1alpha mRNA and protein were increased by obesity. The underlying mechanism was investigated in 3T3-L1 adipocytes. HIF-1alpha mRNA and protein were augmented by adipocyte differentiation. In differentiated adipocytes, insulin further enhanced HIF-1alpha in both levels. Hypoxia enhanced only HIF-1alpha protein, not mRNA. PI3K and mTOR activities are required for the HIF-1alpha expression. Function of HIF-1alpha protein was investigated in the regulation of VEGF gene transcription. ChIP assay shows that HIF-1alpha binds to the proximal hypoxia response element in the VEGF gene promoter, and its function is inhibited by a corepressor composed of HDAC3 and SMRT. These observations suggest that of the three obesity-associated factors, all of them are able to augment HIF-1alpha protein levels, but only two (adipogenesis and insulin) are able to enhance HIF-1alpha mRNA activity. Adipose tissue HIF-1alpha activity is influenced by multiple signals, including adipogenesis, insulin, and hypoxia in obesity. The transcriptional activity of HIF-1alpha is inhibited by HDAC3-SMRT corepressor in the VEGF gene promoter. |
