| First Author | Robertson CL | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 29 | Pages | 18227-36 |
| PubMed ID | 26070567 | Mgi Jnum | J:223753 |
| Mgi Id | MGI:5660157 | Doi | 10.1074/jbc.M115.661801 |
| Citation | Robertson CL, et al. (2015) Astrocyte Elevated Gene-1 (AEG-1) Regulates Lipid Homeostasis. J Biol Chem 290(29):18227-36 |
| abstractText | Astrocyte elevated gene-1 (AEG-1), also known as MTDH (metadherin) or LYRIC, is an established oncogene. However, the physiological function of AEG-1 is not known. To address this question, we generated an AEG-1 knock-out mouse (AEG-1KO) and characterized it. Although AEG-1KO mice were viable and fertile, they were significantly leaner with prominently less body fat and lived significantly longer compared with wild type (WT). When fed a high fat and cholesterol diet (HFD), WT mice rapidly gained weight, whereas AEG-1KO mice did not gain weight at all. This phenotype of AEG-1KO mice is due to decreased fat absorption from the intestines, not because of decreased fat synthesis or increased fat consumption. AEG-1 interacts with retinoid X receptor (RXR) and inhibits RXR function. In enterocytes of AEG-1KO mice, we observed increased activity of RXR heterodimer partners, liver X receptor and peroxisome proliferator-activated receptor-alpha, key inhibitors of intestinal fat absorption. Inhibition of fat absorption in AEG-1KO mice was further augmented when fed an HFD providing ligands to liver X receptor and peroxisome proliferator-activated receptor-alpha. Our studies reveal a novel role of AEG-1 in regulating nuclear receptors controlling lipid metabolism. AEG-1 may significantly modulate the effects of HFD and thereby function as a unique determinant of obesity. |
