| First Author | Lodhi IJ | Year | 2012 |
| Journal | Cell Metab | Volume | 16 |
| Issue | 2 | Pages | 189-201 |
| PubMed ID | 22863804 | Mgi Jnum | J:299363 |
| Mgi Id | MGI:6492005 | Doi | 10.1016/j.cmet.2012.06.013 |
| Citation | Lodhi IJ, et al. (2012) Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARgamma activation to decrease diet-induced obesity. Cell Metab 16(2):189-201 |
| abstractText | De novo lipogenesis in adipocytes, especially with high fat feeding, is poorly understood. We demonstrate that an adipocyte lipogenic pathway encompassing fatty acid synthase (FAS) and PexRAP (peroxisomal reductase activating PPARgamma) modulates endogenous PPARgamma activation and adiposity. Mice lacking FAS in adult adipose tissue manifested increased energy expenditure, increased brown fat-like adipocytes in subcutaneous adipose tissue, and resistance to diet-induced obesity. FAS knockdown in embryonic fibroblasts decreased PPARgamma transcriptional activity and adipogenesis. FAS-dependent alkyl ether phosphatidylcholine species were associated with PPARgamma and treatment of 3T3-L1 cells with one such ether lipid increased PPARgamma transcriptional activity. PexRAP, a protein required for alkyl ether lipid synthesis, was associated with peroxisomes and induced during adipogenesis. PexRAP knockdown in cells decreased PPARgamma transcriptional activity and adipogenesis. PexRAP knockdown in mice decreased expression of PPARgamma-dependent genes and reduced diet-induced adiposity. These findings suggest that inhibiting PexRAP or related lipogenic enzymes could treat obesity and diabetes. |
