Overexpression of Uncoupling Protein 2 Alters Metabolism

Open Access
- Author:
- Montanez, Jessica Elizabeth
- Graduate Program:
- Pathobiology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- None
- Committee Members:
- Andrew David Patterson, Thesis Advisor/Co-Advisor
- Keywords:
- UCP2
Metabolomics
GC-MS
1H-NMR - Abstract:
- Uncoupling protein 2 (UCP2) is a mitochondrial anion transporter that is ubiquitously expressed throughout the body. UCP2 is thought to uncouple the inner mitochondrial proton gradient from the production of ATP and has been shown to have a protective effect in the pathogenesis of various metabolic disorders such as atherosclerosis, diabetes, and steatosis. However, the mechanism by which UCP2 protects against disease is unknown, but the common, unifying factor appears to be the regulation of ROS. The attenuation of ROS by UCP2 is thought to improve fatty acid catabolism that may protect from mitochondrial dysfunction. Here, we show differences in metabolism associated with overexpression of UCP2 and two UCP2 variants, A55V (an obesity- associated variant of UCP2) and D28N (a dominant negative variant of UCP2), in Cos-7 cells using a combination of molecular biology, biochemistry, and cutting edge mass spectrometry- and NMR-based metabolomics. These variants have been reported to be associated with decreased UCP2 activity. Herein, as demonstrated by GC-MS analysis, three metabolites were found to be significantly decreased in cells overexpressing UCP2: palmitoleate, cholesterol, and inositol. By 1H NMR analysis, two metabolites, choline and succinate, were found to be significantly changed. These metabolite changes associated with UCP2 and their metabolic consequence with respect to a potential role in obesity development will be discussed.