Myricanol modulates skeletal muscle-adipose tissue crosstalk to alleviate high-fat diet-induced obesity and insulin resistance
Myricanol modulates skeletal muscle-adipose tissue crosstalk to alleviate high-fat diet-induced obesity and insulin resistance
复制标题
杨梅醇调节骨骼肌-脂肪串扰以减轻高脂肪饮食引起的肥胖和胰岛素抵抗
DOI：
10.1111/bph.14802
复制
发表时间：
2019-10-14
影响因子：
7.3
通讯作者：
Lin, Ligen
中科院分区：
文献类型：
--
作者：
Shen, Shengnan;Liao, Qiwen;Lin, Ligen
背景和目的骨骼肌是葡萄糖处理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相互作用对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-脂肪组织串扰改善胰岛素敏感性和减轻肥胖。实验方法观察杨梅醇对棕榈酸（PA）处理的小鼠C2C12肌管和高脂饲料（HFD）的治疗作用。采用Transwell法测定肌管与脂肪细胞间的串扰。尼罗红染色检测细胞脂质含量。采用MitoTracker Green染色法和柠檬酸合成酶活性法检测线粒体含量，海马法检测线粒体功能。Western blot检测线粒体相关蛋白和胰岛素信号通路蛋白的表达，elisa试剂盒检测鸢尾素水平。在pa处理的C2C12肌管中，Myricanol通过激活amp激活的蛋白激酶增加线粒体数量和功能，导致脂质积累减少，胰岛素刺激的葡萄糖摄取增强。此外，杨梅醇刺激了肌管中鸢尾素的产生和分泌，从而降低了3T3-L1脂肪细胞中的脂质含量。在饲喂hfd的小鼠中，杨梅醇处理通过提高骨骼肌的脂质利用和鸢尾素的产生以及诱导腹股沟脂肪褐变来减轻肥胖和胰岛素抵抗。结论与意义杨梅醇可调节骨骼肌与脂肪组织的相互作用，刺激脂肪组织褐变，改善骨骼肌的胰岛素敏感性。杨梅醇可能是治疗胰岛素抵抗和肥胖的潜在候选药物。
Background and Purpose 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. Experimental Approach 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. Key Results 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. Conclusions and Implications 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.