| First Author | Liu S | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 4 | Pages | 1005-1018 |
| PubMed ID | 28122227 | Mgi Jnum | J:254345 |
| Mgi Id | MGI:6103032 | Doi | 10.1016/j.celrep.2016.12.086 |
| Citation | Liu S, et al. (2017) Protection against High-Fat-Diet-Induced Obesity in MDM2(C305F) Mice Due to Reduced p53 Activity and Enhanced Energy Expenditure. Cell Rep 18(4):1005-1018 |
| abstractText | The RPL11-MDM2 interaction constitutes a p53 signaling pathway activated by deregulated ribosomal biosynthesis in response to stress. Mice bearing an MDM2(C305F) mutation that disrupts RPL11-MDM2 binding were analyzed on a high-fat diet (HFD). The Mdm2(C305F/C305F) mice, although phenotypically indistinguishable from wild-type (WT) mice when fed normal chow, demonstrated decreased fat accumulation along with improved insulin sensitivity and glucose tolerance after prolonged HFD feeding. We found that HFD increases expression of c-MYC and RPL11 in both WT and Mdm2(C305F/C305F) mice; however, p53 was induced in WT but not in Mdm2(C305F/C305F) mice. Reduced p53 activity in HFD-fed Mdm2(C305F/C305F) mice resulted in higher levels of p53 downregulated targets GLUT4 and SIRT1, leading to increased biosynthesis of NAD(+), and increased energy expenditure. Our study reveals a role for the RPL11-MDM2-p53 pathway in fat storage during nutrient excess and suggests that targeting this pathway may be a potential treatment for obesity. |
