Fibroblast Growth Factor 21 Suppresses Adipogenesis in Pig Intramuscular Fat Cells.
Fibroblast Growth Factor 21 Suppresses Adipogenesis in Pig Intramuscular Fat Cells.
复制标题
DOI：
10.3390/ijms17010011
复制
发表时间：
2015-12-23
影响因子：
5.6
通讯作者：
Xiong Y
中科院分区：
文献类型：
--
作者：
Wang Y;Liu X;Hou L;Wu W;Zhao S;Xiong Y
成纤维细胞生长因子 21 (FGF21) 在治疗与肌肉胰岛素抵抗相关的疾病中发挥着重要作用，其特征在于多种因素，例如肌内甘油三酯 (IMT) 含量。研究还表明，FGF21 可抑制体内甘油三酯的合成。然而，FGF21 调节肌内脂肪 (IMF) 中甘油三酯代谢（可能影响肌肉胰岛素敏感性）的确切机制尚不清楚。为了了解 FGF21 在 IMF 沉积中的作用，我们通过稳定转染在 IMF 细胞中进行 FGF21 过表达。我们的结果表明，FGF21通过减少赖氨酸特异性去甲基化酶1（LSD1）的表达来抑制关键脂肪生成基因过氧化物酶体增殖物激活受体γ（PPARG）、CCAAT/增强子结合蛋白（CEBP）家族的mRNA表达，从而导致脂质积累显着下降，并通过Western blot证实了这一结果。此外，在 FGF21 的触发下，部分脂肪因子——脂肪酸结合蛋白 4 (FABP4)、葡萄糖转运蛋白 4 (GLUT4)、脂联素 (ADIPOQ) 和周脂肪素 (PLIN1)——也被下调。此外，FGF21基因表达被转录因子CEBPβ（CEBPB）抑制，该转录因子对甘油三酯的合成有很大贡献。总而言之，我们的研究首次通过实验证明 FGF21 能够有效阻断 IMF 中的脂肪生成，从而也为 FGF21 改善胰岛素敏感性的机制提供了新的认识。
Fibroblast growth factor 21 (FGF21) plays an important role in the treatment of disease associated with muscle insulin resistance which is characterized by various factors, such as intramuscular triglyceride (IMT) content. Studies have also shown that FGF21 inhibits triglyceride synthesis in vivo. However, the precise mechanism whereby FGF21 regulates triglyceride metabolism in intramuscular fat (IMF), which may influence the muscle insulin sensitivity, is not clearly understood. In order to understand the role of FGF21 in IMF deposition, we performed FGF21 overexpression in IMF cells by stable transfection. Our results showed that FGF21 inhibited the key adipogenesis gene mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG), CCAAT/enhancer-binding protein (CEBP) family by reducing lysine-specific demethylase 1 (LSD1) expression which led to significant decline in lipid accumulation, and the result was confirmed by Western blot. Moreover, triggered by FGF21, parts of the adipokines—fatty acid-binding protein 4 (FABP4), glucose transporter 4 (GLUT4), adiponectin (ADIPOQ), and perilipin (PLIN1)—were also down-regulated. Furthermore, FGF21 gene expression was suppressed by transcription factor CEBP beta (CEBPB) which contributed strongly to triglyceride synthesis. Taken together, our study is the first to experimentally demonstrate FGF21 emerging as an efficient blockade of adipogenesis in IMF, thus also providing a new understanding of the mechanism whereby FGF21 improves insulin sensitivity.