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Astrocyte Elevated Gene-1 (AEG-1) Regulates Lipid Homeostasis
Chadia L Robertson1, Jyoti Srivastava2, Ayesha Siddiq2
1Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298; Departments of Biochemistry, Virginia Commonwealth University, Richmond, Virginia 23298.
The Journal of Biological Chemistry
|June 14, 2015
Summary
Astrocyte elevated gene-1 (AEG-1) knockout mice show reduced body fat and resist weight gain on high-fat diets due to impaired intestinal fat absorption, revealing AEG-1
Area of Science:
- Molecular Biology
- Metabolism
- Genetics
Background:
- Astrocyte elevated gene-1 (AEG-1), also known as metadherin (MTDH) or LYRIC, is recognized as an oncogene.
- The physiological role of AEG-1 in normal biological processes remains largely uncharacterized.
Purpose of the Study:
- To investigate the physiological function of AEG-1.
- To determine the role of AEG-1 in regulating body weight and metabolism.
Main Methods:
- Generation and characterization of AEG-1 knockout (AEG-1KO) mice.
- Phenotypic analysis including body composition, weight gain on high-fat diet (HFD), and intestinal fat absorption.
- Investigation of molecular interactions between AEG-1 and nuclear receptors (RXR, LXR, PPAR-α) in enterocytes.
Main Results:
- AEG-1KO mice exhibited significantly reduced body fat, lower body weight, and extended lifespan compared to wild-type (WT) mice.
- AEG-1KO mice were protected from HFD-induced weight gain, primarily due to decreased intestinal fat absorption.
- AEG-1 was found to interact with retinoid X receptor (RXR), inhibiting its function and the activity of RXR heterodimer partners (LXR, PPAR-α) involved in lipid metabolism.
Conclusions:
- AEG-1 plays a novel role in regulating nuclear receptors that control lipid metabolism.
- AEG-1 acts as a key determinant in modulating the effects of HFD and obesity development.
- Targeting AEG-1 could offer a therapeutic strategy for managing obesity and metabolic disorders.
Keywords:
gene regulationintestinelipidliver metabolismperoxisome proliferator-activated receptor (PPAR)More Related Videos
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