Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.
Diabetes. 2012 Apr;61(4):797-806. doi: 10.2337/db11-0846. Epub 2012 Feb 14.
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.
成纤维细胞生长因子 21（FGF21）可刺激动物的脂肪酸氧化和酮体生成。在这项研究中，我们研究了 FGF21 在丁酸钠（一种饮食组蛋白去乙酰化酶（HDAC）抑制剂）的代谢活性中的作用。向饮食肥胖的 C57BL/6J 小鼠体内注射丁酸钠后，检测血清和肝脏中的 FGF21 表达情况。通过抗体中和或敲除小鼠来确定 FGF21 的作用。研究了 FGF21 在肝脏和 HepG2 肝细胞中的转录情况。三氮唑乙酸（TSA）用作 HDAC 抑制剂的对照。将丁酸钠与 bezafibrate 和 fenofibrate 进行比较，以观察它们对 FGF21 表达的诱导作用。丁酸钠可诱导血清中 FGF21 的表达，增强小鼠体内脂肪酸的氧化，并刺激肝脏中酮体的生成。FGF21 抗体或基因敲除可显著降低丁酸盐的活性。丁酸钠通过抑制抑制过氧化物酶体增殖物激活受体-α功能的 HDAC3，诱导肝脏和肝细胞中 FGF21 基因的表达。丁酸钠增强了 bezafibrate 在诱导 FGF21 表达方面的活性。TSA 表现出与丁酸钠相似的一系列活性。FGF21 介导丁酸盐活性以增加脂肪酸的利用和酮体生成。丁酸钠通过抑制 HDAC3 诱导 FGF21 转录。
