Format

Send to

Choose Destination
J Mol Endocrinol. 2019 Mar 1. pii: JME-18-0259.R2. doi: 10.1530/JME-18-0259. [Epub ahead of print]

MS-275 induces hepatic FGF21 expression via H3K18ac-mediated CREBH signal.

Author information

1
Q Zhang, Department of Endocrinology, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China.
2
Q Zhu, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.
3
D Ruyuan, Gastroenterology and Hepatology, Department of Gastroenterology and Hepatology, Shanghai Institute of Liver disease, Zhongshan Hospital,Fudan University, Shanghai,P.R. China, Shanghai, China.
4
F Zhou, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.
5
L Zhang, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.
6
S Wang, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.
7
K Zhu, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.
8
W Xiao, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
9
Z Libin, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.
10
Q Su, Department of Endocrinology, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China.

Abstract

Fibroblast growth factor 21(FGF21) plays an important role in the regulation of lipid and glucose metabolism. MS-275, as a class I-specific histone deacetylase (HDAC) inhibitor, has also been reported to affect energy metabolism. In this current study, we investigated the effects of MS-275 on hepatic FGF21 expression in vitro and in vivo, and explored whether cAMP-responsive element-binding protein H(CREBH) was involved in the action of MS-275. Our results showed that MS-275 stimulated hepatic FGF21 mRNA and protein expressions in a dose- and time-dependent manner, as well as FGF21 secretion in primary mouse hepatocytes. Serum concentration and hepatic expression of FGF21 were elevated after injection of MS-275, along with increased expressions of genes involved in fatty acid oxidation and ketogenic production (Peroxisome proliferator-activated receptor gammacoactivator1α,PGC-1α; Carnitine palmitoyl-transferase 1a,CPT1a;3-hydroxy-3-methylglutaryl-CoA synthase 2,Hmgcs2) as well as improved blood lipid profile. As a proved transcription factor of FGF21, the expression of CREBH was initiated by MS-275, with increased Histone H3 Lysine 18 acetylation(H3K18ac) signals and hepatocyte nuclear factor 4 alpha (HNF-4α) recruitment in CREBH promoter. Adenovirus-mediated knockdown of CREBH abolished MS-275-induced hepatic FGF21 and lipid metabolism-related gene expressions.These results suggest that MS-275 induces hepatic FGF21 by H3K18ac-mediated CREBH expression.

PMID:
30893641
DOI:
10.1530/JME-18-0259

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center