title: Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals.
abstract: In adipocytes, oxidative stress and chronic inflammation are closely associated with metabolic disorders, including insulin resistance, obesity, cardiovascular disease, and type 2 diabetes. However, the molecular mechanisms underlying these metabolic disorders have not been thoroughly elucidated. In this report, we demonstrate that overexpression of glucose-6-phosphate dehydrogenase (G6PD) in adipocytes stimulates oxidative stress and inflammatory responses, thus affecting the neighboring macrophages. Adipogenic G6PD overexpression promotes the expression of pro-oxidative enzymes, including inducible nitric oxide synthase and NADPH oxidase, and the activation of nuclear factor-kappaB (NF-kappaB) signaling, which eventually leads to the dysregulation of adipocytokines and inflammatory signals. Furthermore, secretory factors from G6PD-overexpressing adipocytes stimulate macrophages to express more proinflammatory cytokines and to be recruited to the adipocytes; this would cause chronic inflammatory conditions in the adipose tissue of obesity. These effects of G6PD overexpression in adipocytes were abolished by pretreatment with NF-kappaB inhibitors or antioxidant drugs. Thus, we propose that a high level of G6PD in adipocytes may mediate the onset of metabolic disorders in obesity by increasing the oxidative stress and inflammatory signals.
authors.affiliation: Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul, Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.forename: Sung Sik
authors.initials: SS
authors.lastname: Choe
authors.forename: A Hyun
authors.initials: AH
authors.lastname: Choi
authors.forename: Kang Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Myeong Jin
authors.initials: MJ
authors.lastname: Yoon
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000273:Adipose Tissue / Q000503:physiopathology; D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005786:Gene Expression Regulation; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II; D009765:Obesity / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D005954:Glucosephosphate Dehydrogenase; D052247:Nitric Oxide Synthase Type II