【摘要】 目的:对比12周高强度间歇训练与中等强度持续训练促进肥胖小鼠内脏与皮下白色脂肪棕色化的效果,分析促进棕色化的交感神经活动及肌肉因子合成与棕色化标志物的相关关系。随后根据相关分析结果,对内脏脂肪交感神经受体进行化学抑制,验证交感神经活动促棕色化的作用。方法:1)效果观察实验,采用雌性C57bl/6小鼠经高糖高脂膳食诱导建立肥胖动物模型后,随机分为肥胖对照组(HFD)、中等强度持续运动组(MICT)和高强度间歇训练组(HIIT),HFD组不运动,MICT组进行中等强度跑台训练,HIIT组进行高强度间歇跑台训练。训练周期12周,期间3组均继续进行高糖高脂饲养。训练结束后测量子宫周围内脏脂肪与腹股沟皮下脂肪重量,H.E.染色观察脂肪细胞形态,蛋白免疫印迹观察骨骼肌过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator-activated receptor gamma coactivator 1-alpha,PGC-1α)、纤维连接蛋白Ⅲ型结构域蛋白5(fibronectin typeⅢdomain-containing protein 5,FNDC5)、脂肪酪氨酸羟化酶(tyrosine hydroxylase,TH)及解偶联蛋白1(uncoupling protein-1,UCP-1)表达;2)机制验证实验,12只小鼠随机分为安慰剂组(Saline)与拮抗剂组(SR),两组均进行10天HIIT训练,SR组每次训练前2 h腹腔注射脂肪交感神经受体拮抗剂SR59230a,Saline组注射生理盐水,训练结束后蛋白免疫印迹观察内脏与皮下脂肪UCP-1表达。结果:1)HIIT组与MICT组体重均非常显著低于HFD组(P<0.01),HIIT组子宫周围内脏脂肪重量显著低于HFD组与MICT组(P<0.05),同时,内脏脂肪细胞体积HIIT组<MICT组<HFD组;HIIT组交感神经标志物TH均高于MICT组(P<0.05或P<0.01);HIIT组内脏脂肪棕色化标志物UCP-1显著高于HFD组与MICT组(P<0.05),同时与TH呈中度相关(R=0.578,P=0.012);MICT组皮下脂肪FNCD5有升高的趋势但个体差异较大无显著性(P>0.05),内脏与皮下脂肪FNDC5与UCP-1均无显著相关性;2)SR组内脏脂肪UCP-1表达显著低于Saline组(P<0.05)。结论:HIIT相比MICT可更显著的促进内脏白色脂肪组织棕色化,且此过程与脂肪交感神经调控密切相关。更多还原

【Abstract】 Objective: To compare the effects of 12-week high-intensity interval training and moderate-intensity continuous training on the visceral and subcutaneous white fat browning in obese mice, and to analyze the browning sympathetic activity and the relationship between muscle factor secretion and browning markers. To verify the role of sympathetic nerve activity in promoting browning by inhibiting visceral fat sympathetic receptors. Methods: 1) observation experiment: obese animal models were established with female C57 bl/6 mice induced by highsugar and high-fat diet. They were randomly divided into high-fat diet(HFD), moderate-intensity continuous training group(MICT) and high-intensity interval training group(HIIT). The training period was 12 weeks, and the three types of groups were continued to be fed with highsugar and fat during the period. At the end of the training, the weight of peri-uterine fat and inguinal fat were measured and HE staining was used to observe the morphology of adipocytes. Western blotting was used to observe peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α), fibronectin type Ⅲ domain-containing protein5(FNDC5), tyrosine hydroxylase(TH)and uncoupling protein-1(UCP-1) expression; 2) mechanism validation experiments, 12 mice were randomly divided into placebo group(Saline) and antagonist group(SR), both groups were trained with HIIT for 10 days. SR mice were intraperitoneally injected with fatty sympathetic receptor antagonist SR59230 a two hours before each training time, and Saline mice were injected with normal saline. After the training, the expression of UCP-1 in the visceral and subcutaneous fat was observed by Western blotting.Results: 1) the body weights of HIIT and MICT group were significantly lower than that of HFD(P<0.01). The peri-uterine fat weights of HIIT were significantly lower than HFD and MICT(P<0.05). The visceral fat cell volume sinascend order were HIIT, MICT, HFD. The sympathetic nerve markers TH in the HIIT group were higher than those in the MICT group(P<0.05 or P<0.01). Browning marker UCP-1 of visceral fat in the HIIT group was significantly higher than HFD and MICT(P<0.05), and visceral fat UCP-1 was moderately correlated with TH(R=0.578, P=0.012); Subcutaneous fat FNCD5 in MICT had an increasing trend but the individual difference was not significant(P>0.05). There was no significant correlation among visceral and subcutaneous fat FNDC5 and UCP-1; 2) the expression of visceral fat UCP-1 in the SR group was significantly lower than Saline group(P<0.05). Conclusion: HIIT can significantly promote the browning of visceral white adipose tissue compared with MICT, and this process is closely related to the regulation of fat sympathetic nerve.更多还原