Endoplasmic reticulum stress induces the expression of fetuin-A to develop insulin resistance

Horng Yih Ou, Hung Tsung Wu, Hao Chang Hung, Yi Ching Yang, Jin Shang Wu, Chih Jen Chang

研究成果: Article

45 引文 斯高帕斯(Scopus)

摘要

Fetuin-A is a biomarker reported to be important in many metabolic disorders, including obesity, diabetes, and hepatic steatosis. Although it is well known that fetuin-A is increased in diabetes and nonalcoholic fatty liver disease (NAFLD), the levels of fetuin-A in diabetic patients with NAFLD are unknown. Furthermore, the regulation of fetuin-A expression is still obscure. In this study, a total of 180 age- and sex-matched subjects with normal glucose tolerance, NAFLD, newly diagnosed diabetes (NDD), and NDD with NAFLD were recruited. We found that the levels of fetuin-A were significantly increased in NDD with NAFLD as compared with NDD or NAFLD subjects. We further used HepG2 cells to investigate the regulation of fetuin-A. Treatment with endoplasmic reticulum (ER) stress activator, thapsigargin, increased the expression of fetuin-AmRNA and protein in a time-and dose-dependent manner. Pretreatment with ER stress inhibitor, 4-phenylbutyrate, reversed high glucose or palmitate-induced fetuin-A expression. Moreover, treatment with 4-phenylbutyrate in both streptozotocin-induced and high-fat diet-induced diabetic mice not only decreased hepatic fetuin-A levels but also improved hyperglycemia. Taken together, we found that fetuin-A levels were increased in diabetes patients with NAFLD. Moreover, ER stress induced by high glucose and palmitate increased the expression of fetuin-A and further contributed to the development of insulin resistance.

原文English
頁(從 - 到)2974-2984
頁數11
期刊Endocrinology
153
發行號7
DOIs
出版狀態Published - 2012 七月

All Science Journal Classification (ASJC) codes

  • Endocrinology

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