Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China.
Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China.
J Nutr Biochem. 2024 Jan;123:109507. doi: 10.1016/j.jnutbio.2023.109507. Epub 2023 Oct 26.
In recent years, the impact of bile acids and their representative G protein-coupled bile acid receptor 1 Takeda-G-protein-receptor-5 (TGR5) signaling pathway on muscle function and metabolic health has gained considerable interest. Increasing the content of slow muscle fibers has been recognized as an effective strategy to improve metabolic health. Oleanolic acid (OA) is a naturally occurring triterpenoid compound derived from plants, which can activate TGR5. The aim of this study was to investigate the effect of OA and TGR5 on muscle fiber types and further explore the underlying TGR5-dependent mechanisms. In this study, mice were divided into three groups and dietary supplementation with 0, 50, or 100 mg/kg OA. In addition, C2C12 cells were treated with OA at concentrations of 0, 5, 10, and 20 µM. Our studies revealed that OA promoted the conversion of fast to slow muscle fibers. In addition, it was found that OA activated the TGR5-mediated calcineurin (CaN)/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Further mechanistic investigations demonstrated that inhibiting TGR5 and CaN abolished the effects of OA on muscle fiber types transformation. In conclusion, this study found that OA promotes the transformation of fast muscle fibers to slow muscle fibers through the TGR5-mediated CaN/NFATc1 signaling pathway.
近年来，胆汁酸及其代表性的 G 蛋白偶联胆汁酸受体 1（Takeda-G 蛋白受体 5，TGR5）信号通路对肌肉功能和代谢健康的影响引起了广泛关注。增加慢肌纤维含量已被认为是改善代谢健康的有效策略。熊果酸（oleanolic acid，OA）是一种天然存在的植物三萜类化合物，可激活 TGR5。本研究旨在探讨 OA 和 TGR5 对肌纤维类型的影响，并进一步探讨 TGR5 依赖性机制。在这项研究中，将小鼠分为三组，分别用 0、50 或 100mg/kg OA 进行饮食补充。此外，用 0、5、10 和 20μM OA 处理 C2C12 细胞。我们的研究表明，OA 促进了快肌纤维向慢肌纤维的转化。此外，还发现 OA 激活了 TGR5 介导的钙调神经磷酸酶（calcineurin，CaN）/活化 T 细胞的核因子 1（nuclear factor of activated T cells cytoplasmic 1，NFATc1）信号通路。进一步的机制研究表明，抑制 TGR5 和 CaN 可消除 OA 对肌纤维类型转化的影响。综上所述，本研究发现 OA 通过 TGR5 介导的 CaN/NFATc1 信号通路促进快肌纤维向慢肌纤维的转化。
