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ATF3 plays a role in adipocyte hypoxia-mediated mitochondria dysfunction in obesity.

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.
AuthorsMin-Kyung Jang, Yonghae Son, Myeong Ho Jung
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 431 Issue 3 Pg. 421-7 (Feb 15 2013) ISSN: 1090-2104 [Electronic] United States
PMID23333392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Activating Transcription Factor 3
  • Atf3 protein, mouse
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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