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钙调神经磷酸酶-NFAT 通路介导百里香酚对骨骼肌氧化代谢和纤维型转换的影响。

Ca-Calcineurin-NFAT pathway mediates the effect of thymol on oxidative metabolism and fiber-type switch in skeletal muscle.

机构信息

Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, People's Republic of China.

出版信息

Food Funct. 2019 Aug 1;10(8):5166-5173. doi: 10.1039/c8fo02248h. Epub 2019 Aug 5.

DOI:10.1039/c8fo02248h
PMID:31378798
Abstract

Thymol is a major component of thyme, and it has been reported that thymol administration reduces body weight, plasma insulin and blood glucose in type-2 diabetes. Skeletal muscle is the most important metabolism organs in the body; however, to date, there is no report on the effect of thymol on skeletal muscle. Our goal was to determine whether thymol has an effect on the different types of skeletal muscle fibers and their metabolism characteristics. Hence, we performed in vivo and in vitro experiments. In vivo, SD rats (4 weeks old) were fed with different concentrations of thymol for 4 weeks, and in vitro C2C12 myotubes were directly treated with thymol for 2 days. The rats fed with 0.025% thymol showed a significantly lower body weight, subcutaneous white adipose tissue index and gastrocnemius muscle index (P < 0.05), while their proportion of brown adipose tissue significantly increased (P < 0.05). The protein and mRNA expression of MyHC I and MyHC IIa in the gastrocnemius muscle of the rats significantly increased (P < 0.05), while the protein level of MyHC II and mRNA expression of MyHC IIb decreased (P < 0.05). Furthermore, 0.025% thymol supplement significantly reduced (P < 0.05) the activity of lactate dehydrogenase (LDH) in the gastrocnemius muscle of the rats, but their succinate dehydrogenase (SDH) and hexokinase (HK) activities increased (P < 0.05). Also, the expression of the fatty acid oxidation-related genes in the gastrocnemius muscle of the rats decreased with the thymol supplement (P < 0.05). In vitro, similar results were obtained. Furthermore, the Ca-calcineurin-NFAT pathway, which is an important pathway to regulate the transformation of skeletal muscle fiber type, was studied. We found that the effects of thymol on the myosin heavy chain isoforms, genes related to metabolism and the activation of the Ca-calcineurin-NFAT pathway were all reversed by a Ca chelator (P < 0.05). Thus, thymol can promote the oxidative metabolism and fiber type switch in skeletal muscle, and the Ca-calcineurin-NFAT pathway plays an important role in it.

摘要

百里香酚是百里香的主要成分,据报道,百里香酚的给药可以降低 2 型糖尿病患者的体重、血浆胰岛素和血糖。骨骼肌是人体最重要的代谢器官;然而,迄今为止,尚无关于百里香酚对骨骼肌的影响的报道。我们的目标是确定百里香酚是否对不同类型的骨骼肌纤维及其代谢特征有影响。因此,我们进行了体内和体外实验。在体内,SD 大鼠(4 周龄)用不同浓度的百里香酚喂养 4 周,体外 C2C12 肌管直接用百里香酚处理 2 天。用 0.025%百里香酚喂养的大鼠体重、皮下白色脂肪组织指数和比目鱼肌指数明显降低(P<0.05),而棕色脂肪组织的比例明显增加(P<0.05)。大鼠比目鱼肌中肌球蛋白重链 I 和肌球蛋白重链 IIa 的蛋白和 mRNA 表达明显增加(P<0.05),而肌球蛋白重链 II 的蛋白水平和肌球蛋白重链 IIb 的 mRNA 表达降低(P<0.05)。此外,0.025%百里香酚补充显著降低(P<0.05)大鼠比目鱼肌中乳酸脱氢酶(LDH)的活性,但琥珀酸脱氢酶(SDH)和己糖激酶(HK)的活性增加(P<0.05)。此外,大鼠比目鱼肌中与脂肪酸氧化相关的基因表达随着百里香酚的补充而减少(P<0.05)。在体外,也得到了类似的结果。此外,研究了钙调神经磷酸酶-NFAT 通路,这是调节骨骼肌纤维类型转化的重要通路。我们发现,百里香酚对肌球蛋白重链同工型、代谢相关基因和钙调神经磷酸酶-NFAT 通路的激活的影响都被钙螯合剂逆转(P<0.05)。因此,百里香酚可以促进骨骼肌的氧化代谢和纤维类型转换,钙调神经磷酸酶-NFAT 通路在其中发挥重要作用。

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