State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China.
Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Br J Pharmacol. 2019 Oct;176(20):3983-4001. doi: 10.1111/bph.14802. Epub 2019 Oct 14.
Skeletal muscle is the predominant site for glucose disposal and fatty acid consumption. Emerging evidence indicates that the crosstalk between adipose tissue and skeletal muscle is critical in maintaining insulin sensitivity and lipid homeostasis. The current study was designed to investigate whether myricanol improves insulin sensitivity and alleviates adiposity through modulating skeletal muscle-adipose tissue crosstalk.
The therapeutic effect of myricanol was evaluated on palmitic acid (PA)-treated C2C12 myotubes and high-fat diet (HFD)-fed mice. The crosstalk between myotubes and adipocytes was evaluated using Transwell assay. The cellular lipid content was examined by Nile red staining. The mitochondrial content was assessed by MitoTracker Green staining and citrate synthase activity, and the mitochondrial function was examined by Seahorse assay. Expression of mitochondria-related and insulin signalling pathway proteins was analysed by Western blot, and the irisin level was determined by elisa kit.
Myricanol increased mitochondrial quantity and function through activating AMP-activated protein kinase, resulting in reduced lipid accumulation and enhanced insulin-stimulated glucose uptake, in PA-treated C2C12 myotubes. Furthermore, myricanol stimulated irisin production and secretion from myotubes to reduce lipid content in 3T3-L1 adipocytes. In HFD-fed mice, myricanol treatment alleviated adiposity and insulin resistance through enhancing lipid utilization and irisin production in skeletal muscle and inducing browning of inguinal fat.
Myricanol modulates skeletal muscle-adipose tissue crosstalk, to stimulate browning of adipose tissue and improve insulin sensitivity in skeletal muscle. Myricanol might be a potential candidate for treating insulin resistance and obesity.
骨骼肌是葡萄糖摄取和脂肪酸消耗的主要部位。新出现的证据表明，脂肪组织和骨骼肌之间的串扰对于维持胰岛素敏感性和脂质稳态至关重要。本研究旨在探讨杨梅醇是否通过调节骨骼肌-脂肪组织串扰来改善胰岛素敏感性和减轻肥胖。
用棕榈酸（PA）处理 C2C12 肌管和高脂肪饮食（HFD）喂养的小鼠来评估杨梅醇的治疗效果。使用 Transwell 测定法评估肌管和脂肪细胞之间的串扰。通过尼罗红染色检查细胞脂质含量。通过 MitoTracker Green 染色和柠檬酸合酶活性评估线粒体含量，并通过 Seahorse 测定法检查线粒体功能。通过 Western blot 分析线粒体相关和胰岛素信号通路蛋白的表达，并通过 ELISA 试剂盒测定鸢尾素水平。
杨梅醇通过激活 AMP 激活的蛋白激酶增加线粒体数量和功能，从而减少 PA 处理的 C2C12 肌管中的脂质积累并增强胰岛素刺激的葡萄糖摄取。此外，杨梅醇刺激肌管中鸢尾素的产生和分泌，以减少 3T3-L1 脂肪细胞中的脂质含量。在 HFD 喂养的小鼠中，杨梅醇通过增强骨骼肌中的脂质利用和鸢尾素产生并诱导腹股沟脂肪的褐色化来减轻肥胖和胰岛素抵抗。
杨梅醇调节骨骼肌-脂肪组织串扰，刺激脂肪组织的褐色化并改善骨骼肌中的胰岛素敏感性。杨梅醇可能是治疗胰岛素抵抗和肥胖的潜在候选药物。
