Abstract |
Obesity-associated adipose tissue hypoxia plays a pivotal role in insulin resistance via impaired adipocyte dysfunction including mitochondria dysfunction. In this study, we investigated the involvement of hypoxia-inducible ATF3 in adipocyte hypoxia-mediated mitochondrial dysfunction. While HIF-1α and ATF3 were increased in white adipose tissue of high fat diet (HFD) obese mice compared with control lean mice, mitochondria-related genes were significantly reduced. Treatment with hypoxia mimetics CoCl(2) or incubation with 2% O(2) impaired mitochondria function as demonstrated by decreases in ATP production, NADH dehydrogenase activity, mitochondrial membrane potential, and reduced expression of mitochondria-related genes including NRF-1, PGC-1α, COX1 and SOD in 3T3-L1 adipocyte cells. Furthermore, overexpression of ATF3 in 3T3-L1 cells also decreased mitochondria function as well as expression of mitochondria-related genes. ATF3 knockdown in 3T3-L1 cells partly prevented the hypoxia-mediated decrease in mitochondria function and expression of mitochondria-related genes. The mitochondria-related genes were decreased in white adipose tissue of ATF3-overexpressing mice compared with wild-type mice. These results suggest that ATF3 may play a role in adipocyte hypoxia-mediated mitochondrial dysfunction in obesity.
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Authors | Min-Kyung Jang, Yonghae Son, Myeong Ho Jung |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 431
Issue 3
Pg. 421-7
(Feb 15 2013)
ISSN: 1090-2104 [Electronic] United States |
PMID | 23333392
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
Chemical References |
- Activating Transcription Factor 3
- Atf3 protein, mouse
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Topics |
- 3T3-L1 Cells
- Activating Transcription Factor 3
(genetics, physiology)
- Adipocytes
(metabolism)
- Animals
- Cell Hypoxia
- Down-Regulation
- Gene Expression Regulation
- Genes, Mitochondrial
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Mitochondria
(genetics, metabolism)
- Obesity
(genetics, metabolism)
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