Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):212-7. doi: 10.1016/j.bbrc.2014.10.147. Epub 2014 Nov 5.

Alpha lipoic acid induces hepatic fibroblast growth factor 21 expression via up-regulation of CREBH.

Author information

1
Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu, South Korea.
2
Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu, South Korea. Electronic address: leei@knu.ac.kr.
3
Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu, South Korea. Electronic address: kpark@knu.ac.kr.

Abstract

Hepatic expression of fibroblast growth factor 21 (FGF21), one of the most promising therapeutic candidates for metabolic syndrome, is induced by multiple factors associated with fasting, including cyclic AMP response element-binding protein H (CREBH). Alpha lipoic acid (ALA), a naturally occurring thiol antioxidant, has been shown to induce metabolic changes that are similar to those induced by FGF21, including weight loss and increased energy expenditure. Here, we investigated the effect of ALA on hepatic FGF21 expression. ALA treatment enhanced CREBH and FGF21 mRNA expression and protein abundance in cultured hepatocytes. ALA increased FGF21 promoter activity by up-regulating CREBH expression and increasing CREBH binding to the FGF21 promoter, indicating that ALA up-regulates FGF21 at the transcriptional level. Moreover, inhibition of endogenous CREBH expression by siRNA attenuated ALA-induced FGF21 expression. Finally, treatment of mice with ALA enhanced fasting-induced up-regulation of CREBH and FGF21 in the liver and inhibited feeding-induced suppression of their expression. Consistently, ALA increased serum FGF21 levels in both fasted and fed mice. Collectively, these results indicate that ALA increases hepatic FGF21 expression via up-regulation of CREBH, identifying ALA as a novel positive regulator of FGF21.

KEYWORDS:

Alpha lipoic acid; CREBH; FGF21; Liver

PMID:
25449271
DOI:
10.1016/j.bbrc.2014.10.147
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center