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

Jiyoung Park, Sik Choe Sung, A. Hyun Choi, Ho Kim Kang, Jin Yoon Myeong, Takayoshi Suganami, Yoshihiro Ogawa, Bum Kim Jae

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109 Citations (Scopus)

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 in-flammatory 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-κB (NF-κB) 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-κB 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.

Original languageEnglish
Pages (from-to)2939-2949
Number of pages11
JournalDiabetes
Volume55
Issue number11
DOIs
Publication statusPublished - Nov 1 2006
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Park, J., Sung, S. C., Choi, A. H., Kang, H. K., Myeong, J. Y., Suganami, T., ... Jae, B. K. (2006). Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals. Diabetes, 55(11), 2939-2949. https://doi.org/10.2337/db05-1570