Diao Zhicheng, Jia Shunhua, Itoyama Erina, Yoshioka Hidetugu, Murakami Masaru, Funaba Masayuki
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwakecho, Kyoto, 606-8502, Japan.
State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Sci Rep. 2024 Dec 2;14(1):29857. doi: 10.1038/s41598-024-81272-7.
The expression of uncoupling protein 1 (UCP1), which regulates energy expenditure, is limited to brown/beige adipocytes in most mammals; however, it is also detected in the skeletal muscles of cattle. We previously observed a positive relationship between Ucp1 and fast-twitch myosin heavy chain (Myh) expression in bovine skeletal muscles. In the present study, we explored the regulatory expression of Ucp1 in bovine myogenic cells using cell culture. Vitamin C and high-dose capsaicin, which induce the formation of fast-twitch myotubes in murine myogenic cells, did not stimulate myogenesis in bovine myosatellite cells. Treatment with 4-phenylbutyric acid (PBA), a histone deacetylase inhibitor that enhances histone acetylation, upregulates the expression of all myogenic regulatory factors (MRFs), except Myog, in bovine myogenic cells. Consistent with this, PBA increased the expression levels of acetylated lysine 27 of histone 3 (H3K27), the fast-twitch component MYH1/2, and Ucp1 in bovine myogenic cells. SB203580, an inhibitor of p38 MAP kinase, blocked PBA-induced myogenesis and Ucp1 upregulation. PBA is a butyric acid-related molecule, and cattle produce large amounts of volatile fatty acids (VFAs), including acetic acid, propionic acid, and butyric acid, through ruminal fermentation. Propionic acid treatment stimulated H3K27 acetylation, myogenesis, and Ucp1 induction. Thus, the upregulation of muscular Ucp1 may be related to myogenic stimulation through the modulation of histone acetylation status in cattle; we propose that the cattle-specific expression of muscular UCP1 results from VFA production through ruminal fermentation.
解偶联蛋白1（UCP1）可调节能量消耗，其表达在大多数哺乳动物中仅限于棕色/米色脂肪细胞；然而，在牛的骨骼肌中也能检测到。我们之前观察到牛骨骼肌中Ucp1与快肌肌球蛋白重链（Myh）表达之间存在正相关关系。在本研究中，我们利用细胞培养探索了Ucp1在牛成肌细胞中的调控表达。维生素C和高剂量辣椒素可诱导小鼠成肌细胞形成快肌肌管，但并未刺激牛肌卫星细胞的肌生成。4-苯基丁酸（PBA）是一种组蛋白去乙酰化酶抑制剂，可增强组蛋白乙酰化，它能上调牛成肌细胞中除Myog外的所有成肌调节因子（MRF）的表达。与此一致的是，PBA增加了牛成肌细胞中组蛋白3赖氨酸27乙酰化（H3K27）、快肌成分MYH1/2和Ucp1的表达水平。p38丝裂原活化蛋白激酶抑制剂SB203580可阻断PBA诱导的肌生成和Ucp1上调。PBA是一种与丁酸相关的分子，牛通过瘤胃发酵产生大量挥发性脂肪酸（VFA），包括乙酸、丙酸和丁酸。丙酸处理可刺激H3K27乙酰化、肌生成和Ucp1诱导。因此，肌肉Ucp1的上调可能与通过调节牛组蛋白乙酰化状态来刺激肌生成有关；我们认为肌肉UCP1在牛中的特异性表达是瘤胃发酵产生VFA的结果。
