Phosphorylation of glycogen synthase kinase-3β in metabolically abnormal obesity affects immune stimulation-induced cytokine production

C. L. Yen, W. C. Chao, C. H. Wu, Y. F. Huang, C. S. Chang, Y. S. Tsai, C. F. Lin, C. C. Shieh

研究成果: Article

5 引文 斯高帕斯(Scopus)

摘要

BACKGROUND: Obesity is a severe health problem worldwide, which leads to multiple comorbidities including type 2 diabetes mellitus and cardiovascular diseases. Inflammation has been found to be an important characteristic of adipose tissue in obese subjects. However, obesity is also associated with compromised immune responses to infections and the impact of obesity on immune function has not been fully understood. SUBJECTS/METHODS: To clarify the role of obesity in the immune responses, we investigated the Toll-like receptor (TLR)-induced cytokine secretion by leukocytes from obese and lean subjects. We also investigated the relationship between insulin-induced intracellular signaling and cytokine production using peripheral blood mononuclear cells (PBMCs) and a monocytic cell line THP-1. RESULTS: We found decreased TLR-induced interferon-γ, interleukin-6 (IL-6) and tumor necrosis factor-α secretions and elevated IL-10 secretion by leukocytes from obese subjects when compared with lean controls. PBMCs from obese subjects showed enhanced basal Akt and glycogen synthase kinase-3β (GSK-3 β) phosphorylation, which did not further increase with insulin and lipopolysaccharide (LPS) stimulation. We also found that LPS-induced IκBα degradation was inhibited in PBMCs from obese subjects. By using THP-1 cells with GSK-3β knockdown or cells treated with hyperinsulinemic and high-fatty acid conditions, we found that LPS-induced nuclear factor κB (NF-κB) activation was inhibited and cyclic adenosine monophosphate response element-binding protein (CREB) activation was enhanced. CONCLUSIONS: These findings indicate that GSK-3β is important in the regulation of NF-κB and CREB activation in leukocytes under the metabolic condition of obesity. Our study revealed a key mechanism through which metabolic abnormalities compromise leukocyte functions in people with obesity.

原文English
頁(從 - 到)270-278
頁數9
期刊International Journal of Obesity
39
發行號2
DOIs
出版狀態Published - 2015 二月 11

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

指紋 深入研究「Phosphorylation of glycogen synthase kinase-3β in metabolically abnormal obesity affects immune stimulation-induced cytokine production」主題。共同形成了獨特的指紋。

  • 引用此