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

作者：Jang Min Kyung; Son Yonghae; Jung Myeong Ho^*

来源：Biochemical and Biophysical Research Communications, 2013, 431(3): 421-427.

DOI：10.1016/j.bbrc.2012.12.154

• Obesity
• Adipose tissue hypoxia
• Activating transcription factor (ATF3)
• Mitochondrial dysfunction
• Nuclear respiratory factor 1 (NRF-1)

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-1 alpha 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 CoCl2 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-1 alpha, 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.

• 出版日期2013-2-15