Ca2+-Calcineurin-NFAT pathway mediate the effect of thymol on oxidative metabolism and fiber type switch in skeletal muscle

2019 
Thymol is a major component of thyme which was reported that thymol administration reduced body weight, plasma insulin and blood glucose in type-2 diabetes. While, skeletal muscle is the most important metabolism organ in a body, but there is no report about effect of thymol on skeletal muscle. Our goal was to determine whether thymol has effects on skeletal muscle fiber types and metabolism characteristic. In vivo and in vitro experiments were carried out. 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. Rats fed with 0.025% thymol shows significantly lower body weight, subcutaneous white adipose tissue index and gastrocnemius muscle index(P<0.05), while the proportion of brown adipose tissue were significantly increased (P<0.05). The protein and mRNA expression of MyHC I, MyHC IIa in gastrocnemius muscle were significantly increased (P<0.05), while the protein level of MyHC II and mRNA expression of MyHC IIb was decreased (P<0.05). Furthermore, 0.025% thymol supplement significantly reduced (P<0.05) the activity of lactate dehydrogenase (LDH) in rats’ gastrocnemius muscle, but the activity of succinate dehydrogenase (SDH) and hexokinase (HK) were increased (P<0.05). Also, the expression of fatty acid oxidation related gens in rats’ gastrocnemius muscle was decreased by thymol (P<0.05). In vitro, we get similar results. Furthermore, Ca2+-Calcineurin-NFAT pathway, which is an important pathway to regulate the transformation of skeletal muscle fiber type, was studied. We found the effect of thymol on myosin heavy chain isoforms, genes related to metabolism and the activation of Ca2+-Calcineurin-NFAT pathway were all reversed by Ca2+ chelator (P<0.05). Thymol can promote oxidative metabolism and fiber type switch in skeletal muscle, and Ca2+-Calcineurin-NFAT pathway plays an important role in it.
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