Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals.
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.
Park
Jiyoung
J
Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul, Korea.
Choe
Sung Sik
SS
Choi
A Hyun
AH
Kim
Kang Ho
KH
Yoon
Myeong Jin
MJ
Suganami
Takayoshi
T
Ogawa
Yoshihiro
Y
Kim
Jae Bum
JB
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
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D005954:Glucosephosphate Dehydrogenase; D052247:Nitric Oxide Synthase Type II