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

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2974-2984
Number of pages11
JournalEndocrinology
Volume153
Issue number7
DOIs
Publication statusPublished - Jul 1 2012
Externally publishedYes

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alpha-2-HS-Glycoprotein
Endoplasmic Reticulum Stress
Insulin Resistance
Palmitates
Glucose
Fetuins
Thapsigargin
Liver
Hep G2 Cells
High Fat Diet
Streptozocin
Non-alcoholic Fatty Liver Disease
Hyperglycemia
Obesity
Biomarkers

ASJC Scopus subject areas

  • Endocrinology

Cite this

Endoplasmic reticulum stress induces the expression of fetuin-A to develop insulin resistance. / Ou, Horng Yih; Wu, Hung Tsung; Hung, Hao Chang; Yang, Yi Ching; Wu, Jin Shang; Chang, Chih Jen.

In: Endocrinology, Vol. 153, No. 7, 01.07.2012, p. 2974-2984.

Research output: Contribution to journalArticle

Ou, Horng Yih ; Wu, Hung Tsung ; Hung, Hao Chang ; Yang, Yi Ching ; Wu, Jin Shang ; Chang, Chih Jen. / Endoplasmic reticulum stress induces the expression of fetuin-A to develop insulin resistance. In: Endocrinology. 2012 ; Vol. 153, No. 7. pp. 2974-2984.
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