| First Author | Wang H | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 7 | Pages | 2442-56 |
| PubMed ID | 25605807 | Mgi Jnum | J:252011 |
| Mgi Id | MGI:5923788 | Doi | 10.2337/db14-0528 |
| Citation | Wang H, et al. (2015) Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis. Diabetes 64(7):2442-56 |
| abstractText | Endostatin is a well-known angiogenesis inhibitor. Although angiogenesis has been considered as a potential therapeutic target of obesity, the inhibitory effect of endostatin on adipogenesis and dietary-induced obesity has never been demonstrated. Adipogenesis plays a critical role in controlling adipocyte cell number, body weight, and metabolic profile in a homeostatic state. Here we reveal that endostatin inhibits adipogenesis and dietary-induced obesity. The antiadipogenic mechanism of endostatin lies in its interaction with Sam68 RNA-binding protein in the nuclei of preadipocytes. This interaction competitively impairs the binding of Sam68 to intron 5 of mammalian target of rapamycin (mTOR), causing an error in mTOR transcript. This consequently decreases the expression of mTOR, results in decreased activities of the mTOR complex 1 pathway, and leads to defects in adipogenesis. Moreover, our findings demonstrate that the antiangiogenic function of endostatin also contributes to its obesity-inhibitory activity. Through the combined functions on adipogenesis and angiogenesis, endostatin prevents dietary-induced obesity and its related metabolic disorders, including insulin resistance, glucose intolerance, and hepatic steatosis. Thus, our findings reveal that endostatin has a potential application for antiobesity therapy and the prevention of obesity-related metabolic syndromes. |
