目的 基于脂肪可塑性探究大黄素改善肥胖的作用和机制。方法 通过高脂饲养8周建立肥胖小鼠模型，肥胖小鼠随机分为对照组、模型组、大黄素（40、80 mg/kg）组、CL316243（1 mg/kg）组和罗格列酮（10 mg/kg）组，连续给药4周。测量各组小鼠体质量，检测Lee’s指数和皮下腹股沟白色脂肪组织（inguinal white adipose tissue，iWAT）、附睾白色脂肪组织（epididymal white adipose tissue，eWAT）、肾周白色脂肪组织（perirenal white adipose tissue，pWAT）、肩胛区棕色脂肪组织（brown adipose tissue，BAT）指数，测量肩胛骨体温；检测口服葡萄糖耐受量、血糖曲线下面积（area under curve，AUC）及血清中总胆固醇（total cholesterol，TC）、三酰甘油（triglyceride，TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）水平；采用苏木素-伊红（HE）染色观察脂肪组织病理变化；免疫组化法检测脂肪组织中棕色化相关蛋白解偶联蛋白1（uncoupling protein 1，UCP1）表达；Western blotting检测皮下iWAT中脂肪可塑性相关蛋白葡萄糖转运蛋白4（glucose transporter 4，GLUT4）、过氧化物酶体增殖物激活受体γ共激活剂-1α（peroxisome proliferator-activated receptor-gamma coactivator-1α，PGC-1α）、PR结构域蛋白16（positive regulatory domain-containing 16，PRDM16）、线粒体转录因子A（mitochondrial transcription factor A，TFAM）、腺苷酸活化蛋白激酶（AMP-dependent/activated protein kinase，AMPK）、磷酸化AMPK（phosphorylated AMPK，p-AMPK）蛋白表达。结果 与模型组比较，大黄素组小鼠体质量、Lee’s指数及皮下iWAT、eWAT、pWAT指数均显著降低（P＜0.05、0.01、0.001），肩胛区体温升高（P＜0.01），血糖和血清中TC、TG、LDL-C水平均显著降低（P＜0.05、0.01、0.001）；BAT中UCP1表达显著增加（P＜0.001），皮下iWAT中PGC-1α、PRDM16、TFAM、p-AMPK/AMPK、GLUT4蛋白表达水平均显著升高（P＜0.05、0.01）。结论 大黄素能够有效抑制肥胖小鼠模型的体质量增加，改善糖脂代谢紊乱，其机制与激活BAT、诱导WAT棕色化有关。

Objective To study the effect and mechanisms of emodin on obese mice based on fat plasticity. Methods An obese mouse model was established by high-fat feeding for eight weeks. The obese mice were randomly divided into control group, model group, emodin (40, 80 mg/kg) groups, CL316243 (1 mg/kg) group and rosiglitazone (10 mg/kg) group, and were administered continuously for four weeks. Body weight, Lee’s index and indexes of inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT), perirenal white adipose tissue (pWAT) and brown adipose tissue (BAT) in scapular area were measured; Temperature in scapula of mice in each group was measured; Oral glucose tolerance, blood glucose of area under curve (AUC), and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) levels in serum were detected; Hematoxylin eosin (HE) staining was used to observe pathological changes in adipose tissue; Immunohistochemical method was used to detect the expression of uncoupling protein 1 (UCP1) related to browning in adipose tissue; Western blotting was used to detect the expressions of fat plasticity related proteins glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), positive regulatory domain-containing 16 (PRDM16), mitochondrial transcription factor A (TFAM), AMP-dependent/activated protein kinase (AMPK) and phosphorylated AMPK (p-AMPK) in iWAT. Results Compared with model group, body weight, Lee’s index and indexes of iWAT, eWAT and pWAT in emodin group were significantly reduced (P < 0.05, 0.01, 0.001), while the temperature in scapular area was increased (P < 0.01). Blood glucose and levels of TC, TG and LDL-C in serum were significantly reduced (P < 0.05, 0.01, 0.001); UCP1 expression was significantly increased in BAT (P < 0.001), while PGC1-1α, PRDM16, TFAM, p-AMPK/AMPK and GLUT4 protein expressions in iWAT were significantly increased (P < 0.05, 0.01). Conclusion Emodin can effectively inhibit the increase in body weight and improve glucose and lipid metabolism disorders in obese mouse models. Its mechanism is related to the activation of BAT and induction of browning of WAT.

国家自然科学基金资助项目（81503287）