| First Author | Lu Z | Year | 2013 |
| Journal | EMBO J | Volume | 32 |
| Issue | 6 | Pages | 844-57 |
| PubMed ID | 23403926 | Mgi Jnum | J:195318 |
| Mgi Id | MGI:5477888 | Doi | 10.1038/emboj.2013.25 |
| Citation | Lu Z, et al. (2013) pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location. EMBO J 32(6):844-57 |
| abstractText | pRb is frequently inactivated in tumours by mutations or phosphorylation. Here, we investigated whether pRb plays a role in obesity. The Arcuate nucleus (ARC) in hypothalamus contains antagonizing POMC and AGRP/NPY neurons for negative and positive energy balance, respectively. Various aspects of ARC neurons are affected in high-fat diet (HFD)-induced obesity mouse model. Using this model, we show that HFD, as well as pharmacological activation of AMPK, induces pRb phosphorylation and E2F target gene de-repression in ARC neurons. Some affected neurons express POMC; and deleting Rb1 in POMC neurons induces E2F target gene de-repression, cell-cycle re-entry, apoptosis, and a hyperphagia-obesity-diabetes syndrome. These defects can be corrected by combined deletion of E2f1. In contrast, deleting Rb1 in the antagonizing AGRP/NPY neurons shows no effects. Thus, pRb-E2F1 is an obesity suppression mechanism in ARC POMC neurons and HFD-AMPK inhibits this mechanism by phosphorylating pRb in this location. |
