胰岛素抵抗是肥胖和2型糖尿病的关键病理基础。胰岛素靶器官脂肪组织SIRT1/PPARγ激活后，调控脂肪细胞分化及脂质代谢，改善脂质沉积和胰岛素敏感性，成为肥胖和2型糖尿病的分子靶点。我们前期研究发现电针可减少胰岛素抵抗模型大鼠体重和摄食量，激活股四头肌SIRT1/PGC-1α及下游线粒体生物合成和氧化相关基因，增强线粒体氧化呼吸功能，有效提高胰岛素敏感性。本项目拟采用电针干预胰岛素抵抗肥胖模型大鼠，运用荧光素酶报告基因技术、RT-PCR、免疫荧光双标、Western blotting等技术，观察电针对不同脂肪组织SIRT1/PPARγ及下游脂肪细胞分化和脂质代谢基因表达的影响，并与SIRT1激动剂白藜芦醇对照，探讨电针可能通过调控脂肪组织SIRT1/ PPARγ影响脂肪细胞分化及脂质代谢和胰岛素抵抗的机制。本项目的完成将为临床运用电针治疗胰岛素抵抗肥胖及其相关疾病提供新的实验依据。

Insulin resistance (IR) is a key pathological mechanism of obesity and type 2 diabetes (T2DM) in early state. In insulin target organ adipose tissue, SIRT1 activates PPARγ regulating adipocyte differentiation, modulating lipid metabolism, improving lipid deposition and insulin sensitivity. Thus it becomes molecular target for the treatment of obesity and T2DM. Our previous research demonstrated that electroacupuncture could control the body mass increase of high-fat-diet-induced IR rat model and reduce food intake, effectively improve insulin sensitivity by stimulating SIRT1/PGC-1α in the femoral quadriceps muscle, activating downstream of mitochondrial biogenesis and oxidation related gene expression, enhancing the quadriceps muscle mitochondrial function. In this study we will intervene high-fat-diet-induced IR obese rat model by electroacupuncture. Dual-luciferase Reporter Assay, RT-PCR, Double immunofluorescence techniques and Western blotting will be applied to measure the lipid metabolism gene transcription, mRNA and protein expression, the different adipose tissue SIRT1 /PPARγ activation and downstream adipocyte differentiation will be observed as well. The SIRT1 activator resveratrol gavage as control compares the effects of electroacupuncture. The aim of the study is to investigate the possible mechanism of electroacupuncture in modulating adipose tissue SIRT1/PPARγ affected adipocyte differentiation, the lipid metabolism and IR. The study will provide new experimental evidence for clinical application of electroacupuncture in the treatment of IR obesity and related diseases and contribute to the clinical application and promotion of electroacupuncture treating IR obesity.