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Astrocyte Elevated Gene-1 (AEG-1) Regulates Lipid Homeostasis.
- Source :
-
Journal of Biological Chemistry . 7/17/2015, Vol. 290 Issue 29, p18227-18236. 10p. - Publication Year :
- 2015
-
Abstract
- 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-α, 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-α. 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ASTROCYTES
*ONCOGENES
*LABORATORY mice
*RETINOID X receptors
*LIPID metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 290
- Issue :
- 29
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 108590135
- Full Text :
- https://doi.org/10.1074/jbc.M115.661801