Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3.

Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3.
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DOI:
10.2337/db11-0846
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发表时间:
2012-04
期刊:
影响因子:
7.7
通讯作者:
Jia W
Jia W
中科院分区:
医学1区
文献类型:
--
作者:
Li H;Gao Z;Zhang J;Ye X;Xu A;Ye J;Jia W

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成纤维细胞生长因子21(FGF 21)刺激动物脂肪酸氧化和酮体产生。在这项研究中,我们研究了FGF 21在丁酸钠代谢活性中的作用,丁酸钠是一种膳食组蛋白去乙酰化酶(HDAC)抑制剂。将丁酸钠注射到饮食性肥胖的C57 BL/6 J小鼠中后,检测血清和肝脏中的FGF 21表达。使用抗体中和或敲除小鼠确定FGF 21的作用。在肝脏和HepG 2肝细胞中研究FGF 21转录。曲古抑菌素A(TSA)作为HDAC抑制剂用于对照。丁酸酯与苯扎贝特和非诺贝特在诱导FGF 21表达方面进行了比较。丁酸盐诱导血清中的FGF 21,增强小鼠中的脂肪酸氧化,并刺激肝脏中的酮体产生。丁酸盐活性通过FGF 21抗体或基因敲除而显著降低。丁酸通过抑制HDAC 3诱导肝脏和肝细胞中的FGF 21基因表达,HDAC 3抑制过氧化物酶体增殖物激活受体-α功能。丁酸盐增强了苯扎贝特诱导FGF 21的活性。TSA表现出类似的活动丁酸。FGF 21介导丁酸盐活性以增加脂肪酸利用和生酮。丁酸通过抑制HDAC 3诱导FGF 21转录。
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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