| First Author | Wolfrum C | Year | 2003 |
| Journal | J Clin Invest | Volume | 112 |
| Issue | 3 | Pages | 345-56 |
| PubMed ID | 12865419 | Mgi Jnum | J:84920 |
| Mgi Id | MGI:2670809 | Doi | 10.1172/JCI18698 |
| Citation | Wolfrum C, et al. (2003) Role of Foxa-2 in adipocyte metabolism and differentiation. J Clin Invest 112(3):345-56 |
| abstractText | Hepatocyte nuclear factors-3 (Foxa-1-3) are winged forkhead transcription factors that regulate gene expression in the liver and pancreatic islets and are required for normal metabolism. Here we show that Foxa-2 is expressed in preadipocytes and induced de novo in adipocytes of genetic and diet-induced rodent models of obesity. In preadipocytes Foxa-2 inhibits adipocyte differentiation by activating transcription of the Pref-1 gene. Foxa-2 and Pref-1 expression can be enhanced in primary preadipocytes by growth hormone, suggesting that the antiadipogenic activity of growth hormone is mediated by Foxa-2. In differentiated adipocytes Foxa-2 expression leads to induction of gene expression involved in glucose and fat metabolism, including glucose transporter-4, hexokinase-2, muscle-pyruvate kinase, hormone-sensitive lipase, and uncoupling proteins-2 and -3. Diet-induced obese mice with haploinsufficiency in Foxa-2 (Foxa-2+/-) develop increased adiposity compared with wild-type littermates as a result of decreased energy expenditure. Furthermore, adipocytes of these Foxa-2+/- mice exhibit defects in glucose uptake and metabolism. These data suggest that Foxa-2 plays an important role as a physiological regulator of adipocyte differentiation and metabolism. |
