Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3 | Zendy

Huating Li | Zendy; ZhanGuo Gao | Zendy; Jin Zhang | Zendy; Xin Ye | Zendy; Aimin Xu | Zendy; Jianping Ye | Zendy; Weiping Jia | Zendy

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Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3

Author(s) -

Huating Li,

ZhanGuo Gao,

Jin Zhang,

Xin Ye,

Aimin Xu,

Jianping Ye,

Weiping Jia

Publication year - 2012

Publication title -

diabetes

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.219

H-Index - 330

eISSN - 1939-327X

pISSN - 0012-1797

DOI - 10.2337/db11-0846

Subject(s) - fgf21 , sodium butyrate , butyrate , ketogenesis , chemistry , endocrinology , histone deacetylase inhibitor , medicine , ketone bodies , histone deacetylase , biochemistry , biology , metabolism , fibroblast growth factor , receptor , histone , fermentation , gene

Fibroblast growth factor 21 (FGF21) stimulates fatty acid oxidation and ketone body production in animals. In this study, we investigated the role of FGF21 in the metabolic activity of sodium butyrate, a dietary histone deacetylase (HDAC) inhibitor. FGF21 expression was examined in serum and liver after injection of sodium butyrate into dietary obese C57BL/6J mice. The role of FGF21 was determined using antibody neutralization or knockout mice. FGF21 transcription was investigated in liver and HepG2 hepatocytes. Trichostatin A (TSA) was used in the control as an HDAC inhibitor. Butyrate was compared with bezafibrate and fenofibrate in the induction of FGF21 expression. Butyrate induced FGF21 in the serum, enhanced fatty acid oxidation in mice, and stimulated ketone body production in liver. The butyrate activity was significantly reduced by the FGF21 antibody or gene knockout. Butyrate induced FGF21 gene expression in liver and hepatocytes by inhibiting HDAC3, which suppresses peroxisome proliferator-activated receptor-α function. Butyrate enhanced bezafibrate activity in the induction of FGF21. TSA exhibited a similar set of activities to butyrate. FGF21 mediates the butyrate activity to increase fatty acid use and ketogenesis. Butyrate induces FGF21 transcription by inhibition of HDAC3.

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