基于PGC-1α/Irisin/UCP1信号通路介导的白色脂肪组织棕色化探讨电针治疗肥胖的作用机制

The hotspot of the research is how to control obesity through promoting browning of white adipose tissue. Based on the fact that PGC-1α/Irisin/UCP1 signaling pathway plays an important role in the process of white adipose tissue browning. To further elucidate the action mechanism of acupuncture in losing weight, we intend to take obese rats as the research object. We will apply electroacupuncture, exercise and exercise plusing electroacupuncture intervention respectively to observe their influence on rat’s weight, blood biochemical index, etc. to evaluate the effect of electroacupuncture on losing weight and lipid-reducing in obese rats. We will detect brown fat content, mitochondrial content, activity, aerobic metabolism and related indices of the obese rats after EA to find out whether electroacupuncture can promote white adipose tissue browning. We will also block PGC-1 signaling pathway by siRNA to further clarify the mechanism of PGC-1 alpha /Irisin/UCP1 signaling pathway in electroacupuncture promoting white fat browning.we will observe the synergistic effect of electroacupuncture combined with exercise on promoting browning of white adipose tissue in obese rats, so as to provide evidence for clinical use of electroacupuncture combined with exercise therapy for obesity,and clinical treatment of scheme optimization.

如何通过促进机体白色脂肪组织棕色化来控制肥胖是目前研究的热点，基于PGC-1α/Irisin/UCP1 信号通路在白色脂肪组织棕色化的过程中具有重要作用，为进一步阐明针灸减肥的作用机制，我们拟以肥胖大鼠为研究对象，通过电针、运动及电针结合运动干预，观测对大鼠体格、血生化相关指标等的影响，评价电针对肥胖大鼠的减肥降脂作用；通过检测电针干预后肥胖大鼠棕色脂肪含量、线粒体含量活性有氧代谢等相关指标，评价电针对白色脂肪组织棕色化的促进作用；通过采用siRNA沉默PGC-1α信号通路，进一步明确PGC-1α/Irisin/UCP1信号通路在电针促进白色脂肪棕色化的作用机制；通过观察电针配合运动对肥胖大鼠白色脂肪棕色化的协同作用，为临床采用电针配合运动治疗肥胖提供依据，从而优化临床治疗方案。

白色脂肪组织棕色化是降脂减肥的重要机制之一，基于PGC-1α/Irisin/UCP1信号通路在白色脂肪组织棕色化中的重要作用，本研究以高脂饮食诱导的肥胖大鼠模型为研究对象，通过电针穴位组与非穴位组比较，分析电针对肥胖大鼠体质量、Lee’s指数、脂肪细胞结构及血脂的影响，结果表明电针减肥降脂作用明确，且并非安慰剂效应。运用RT-PCR、Western blot、免疫组化等技术，分析电针对肥胖大鼠脂肪组织PGC-1α/Irisin/UCP1信号通路的影响，结果提示电针减肥可能是通过促进白色脂肪组织棕色化来实现的。同时采用尾静脉注射AAV-PGC-1α病毒，沉默PGC-1α表达，进一步明确了PGC-1α/Irisin/UCP1信号通路在电针促进白色脂肪棕色化中的作用机制。通过电针联合运动组与电针组、运动组对比，检测肥胖大鼠棕色脂肪组织PGC-1α/Irisin/UCP1信号通路相关指标，结果表明电针、运动、电针联合运动均有促进白色脂肪棕色化的作用，且电针联合运动效果更加突出，具有协同作用。利用转录组学技术，筛选出显著富集的差异表达基因及信号通路，从基因水平分析电针联合运动、电针潜在作用机制，为临床降脂减重提供科学依据。