title: 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.
authors: School of Korean Medicine, Pusan National University, 30 Beom-eo ri, Mulguem-eup, Yangsan-si, Gyeongnam, South Korea.
authors: Min-Kyung
authors: MK
authors: Jang
authors: Yonghae
authors: Y
authors: Son
authors: Myeong Ho
authors: MH
authors: Jung
mesh_terms: D041721:3T3-L1 Cells; D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000502:physiology*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D015536:Down-Regulation; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*
chemical_list: D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse