运动、膳食干预对瘦素抵抗大鼠中枢受体后信号通路作用机制的研究

谈艳; 陈文鹤; 郭黎; 孙庆艳

doi:10.16469/j.css.2011.04.001

运动、膳食干预对瘦素抵抗大鼠中枢受体后信号通路作用机制的研究

Mechanism of Exercise and Diet Interventions on Central Posterior Receptor Signaling of Leptin Resistance Rats

摘要

摘要: 目的:观察运动、膳食干预对具有瘦素抵抗现象肥胖大鼠中枢受体后信号通路的影响,探讨SOCS3在瘦素抵抗发生及改善过程中的作用。方法:雄性SD大鼠130只,随机分为对照组10只,建模组120只,分别给予普通标准啮齿类动物饲料和高脂饲料喂养8周。筛选出建模组体重排序前1/3大鼠,测量其血清瘦素水平,随机分为高脂膳食对照组(H16)、高脂膳食运动组(HHE)、普通膳食运动组(HNE)、普通膳食组(HN),原有的空白对照组为N16组,各组大鼠分别给予中等强度的跑台运动干预或膳食干预8周。采用ELISA法测量血清瘦素水平;Western blot法检测下丘脑中LP-Rb、STAT 3、p-STAT 3及SOCS3蛋白水平;实时荧光定量PCR法测定下丘脑SOCS3 mRNA水平。结果:1)HNE、HHE组血清瘦素水平显著性低于H16组(P<0.05),且HNE组显著性低于HHE及HN组(P<0.01);2)H16组下丘脑LP-Rb水平显著低于N16组(P<0.05),HNE及HHE组较H16组有显著性提高;血清瘦素与下丘脑LP-Rb呈微弱负相关性,R值为-0.286(P<0.05);3)运动、膳食干预提高了HNE组与HHE组的p-STAT 3/STAT 3水平,较H16组有显著性差异(P<0.05);4)各组大鼠下丘脑SOCS3 mRNA表达量无显著性差异(P>0.05);HNE组、HHE组SOCS3蛋白水平显著低于H16组(P<0.05);HNE组显著低于N16组(P<0.05),而HHE及HN组显著高于HNE组(P<0.01);大鼠下丘脑SOCS3蛋白水平与血清瘦素浓度呈低度相关,相关系数R值为0.338(P<0.05)。结论:运动联合膳食干预较单独运动或膳食干预可以明显改善中枢瘦素抵抗,其机制可能与降低血清瘦素水平,上调下丘脑中LP-Rb受体蛋白水平;增加下丘脑中JAK2-STAT 3通路中STAT 3磷酸化水平;降低下丘脑中SOCS3蛋白水平有关。

Abstract: Objective:To observe the effect of exercise and diet interventions on central posterior receptor signaling of leptin resistance obese rats in order to study the effect of SOCS3 on leptin resistance.Method:Totally 130 SD male rats were randomly divided into control group(n=10) and model group(n=120).Two groups were fed with common rodent animal feed and high fat diet respectively.After 8 weeks,we selected 1/3 body weight rats ahead in model group,then measure the serum leptin.The model group rats(n=40) were randomized into four groups:high fat diet group(H16),high fat diet and exercise group(HHE),common diet and exercise group(HNE),common diet group(HN).The control group was recorded as N16.Each group rats were given meal intervention or had medium intensity treadmill exercise for 8 weeks.The serum leptin was measured by ELISA.SOCS3,in hypothalamus was observed by Western blot.SOCS3 mRNA in hypothalamus was showed by real time fluorescent quantitation PCR.Result:1) Leptin of HNE,HHE groups were lower than that of H16(P<0.05),and leptin of HNE group was significantly lower than those of HHE,HN groups(P<0.01).2)LP-Rb in hypothalamus of H16 group was lower than that of N16 group(P<0.05);those of HNE,HHE group significantly elevated compared with H16 group(P<0.05);those of HHE,HN groups were lower than that of HNE group(P<0.05).LP-Rb in hypothalamus had weaker negative correlation with leptin,r=-0.286,(P<0.05).3) p-STAT3/STAT3 of HNE,HHE groups elevated because of exercise and diet interventions,compared with H16 group(P<0.05).4) SOCS3 mRNA of each group had no difference(P>0.05).SOCS3 of HNE,HHE group was significantly lower than that of H16(P<0.05),SOCS3 of HNE was lower than that of N16 group(P<0.05).SOCS3 of HHE,HN group was significantly higher than that of HNE(P<0.01).SOCS3 in hypothalamus had low correlation with serum leptin,R=0.338,(P<0.05).Conclusions:Exercise combination with diet invention was better than exercise or diet to improve central leptin resistance,which mechanisms were possible related to following factors:Leptin lowering,LP-Rb in hypothalamus rising.P-STAT in hypothalamus rising.SOCS3 in hypothalamus lowered.

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