Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals

Diabetes. 2006 Nov;55(11):2939-49. doi: 10.2337/db05-1570.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / drug effects
  • Adipocytes / enzymology
  • Adipocytes / physiology*
  • Adipose Tissue / physiopathology
  • Animals
  • Dehydroepiandrosterone / pharmacology
  • Gene Expression Regulation
  • Glucosephosphate Dehydrogenase / genetics*
  • Glucosephosphate Dehydrogenase / metabolism
  • Inflammation / physiopathology*
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / enzymology
  • Macrophages, Peritoneal / physiology
  • Male
  • Mice
  • Nitric Oxide Synthase Type II
  • Obesity / enzymology
  • Obesity / genetics
  • Obesity / physiopathology
  • Oxidative Stress*
  • RNA, Messenger / genetics


  • Lipopolysaccharides
  • RNA, Messenger
  • Dehydroepiandrosterone
  • Glucosephosphate Dehydrogenase
  • Nitric Oxide Synthase Type II