不同减肥方式对雄性肥胖小鼠脂肪组织炎症-芳香化酶轴的影响

Effects of Different Weight Loss Methods on the Inflammatory-aromatase Axis in Adipose Tissue of Male Obese Mice

目的:探究有氧运动或降脂饮食干预对雄性肥胖小鼠脂肪组织雄激素芳香化作用的影响。方法:3周龄雄性C57BL/6小鼠,按体重随机分为正常饮食组(N组,n=8)和高脂饮食组(F组,n=32)。其中N组正常饮食,F组为高脂饮食。造肥胖模型成功,剔除肥胖未达标小鼠8只后,F组按体重随机分为高脂饮食对照组(FO组,n=8)、高脂饮食运动组(FE组,n=8)、高脂饮食转正常饮食组(FN组,n=8)。FO组持续高脂饮食,不运动。FE组高脂饮食,进行中等强度跑台运动,跑速、运动时间和频率递增,3后周恒定为跑速20 m/min,每天运动60 min,每周运动6天。FN组改为正常饮食,不运动。运动和饮食干预为期8周。末次运动后36~40小时,并禁食12小时后,称量体重,测量体长,取眼球血、腹腔脂肪和腓肠肌。计算Lee’s指数、体脂百分比和肌肉质量指数。ELISA法测试血清和脂肪组织睾酮、雌二醇、白介素6(IL6)、肿瘤坏死因子α(TNFα)。Western Blot法测试脂肪组织芳香化酶、IL6受体α(IL6-Rα)、TNF受体1(TNF-R1)的蛋白表达。结果:(1)FO组血清和脂肪组织IL6和TNFα高于N组(P<0.05),脂肪组织睾酮、雌二醇、芳香化酶、TNF-R1高于N组(P<0.05),血清睾酮低于N组(P<0.05);FO组体重、体脂百分比、进食量、摄入热量、Lee’s指数和血清雌二醇高于N组(P<0.01)。(2)经过8周有氧运动后,FE组体重低于FO组,脂肪组织睾酮、雌二醇、IL6、TNFα和血清雌二醇,脂肪组织芳香化酶和TNF-R1蛋白表达低于FO组(P<0.05);FE组进食量、摄入热量、腹腔脂肪重量、体脂百分比低于FO组(P<0.01)。(3)经过8周饮食干预后,FN组Lee’s指数,血清雌二醇,脂肪组织TNF-R1蛋白表达低于FO组(P<0.05);FN组体重、进食量、摄入热量、腹腔脂肪重量,体脂百分比,脂肪组织睾酮、雌二醇、IL6和TNFα低于FO组(P<0.01)。结论:(1)高脂饮食诱发肥胖会引起雄性小鼠脂肪组织炎症因子和芳香化酶表达增加,进而引起机体雌激素水平升高。(2)有氧运动可能主要通过TNFα-TNFR1途径降低了雄性肥胖小鼠脂肪组织芳香化酶的表达,并且有助于脂肪组织雄激素芳香化作用恢复平衡。(3)降脂饮食干预可能并不是主要通过脂肪组织炎症-芳香化酶途径影响雄性肥胖小鼠的性激素水平。

Objective To investigate the effect of the aerobic exercise or lipid-lowering diet on the androgen aromatization in adipose tissues of male obese mice.Methods Forty three-week-old male C57 BL/6 mice were randomly divided into a normal diet group(group N,n=8)and a high-fat diet group(group F,n=32)according to their body weight.Group N was on a normal diet,while group F was on a high-fat diet.After the successful establishment of the obesity model,the F group was randomly further divided into a high-fat diet control group(group FO,n=8),a high-fat diet exercise group(group FE,n=8)and a high-fat diet to normal diet group(group FN,n=8)according to their body weight after the elimination of 8 mice not meeting the standard of body weight.The FO group maintained a high-fat diet and did not exercise,while the FE group maintained a high-fat diet and a moderate-intensity treadmill exercise with increasing running speed,time and frequency.After three weeks,the running speed was set at 20 m/min,60 minutes a day,6 days a week.The FN group went on a normal diet without any exercise.The exercise and diet interventions lasted for eight weeks.Thirty-six to forty hours after the last exercise,and 12 hours after fasting,the body weight and length were measured,and the eyeball blood,abdominal fat and gastrocnemius muscle were taken to calculate the Lee’s index,body fat percentage and muscle mass index.The serum and adipose tissue testosterone,estradiol,interleukin-6(IL6),tumor necrosis factorα(TNFα)were measured using the enzyme-linked immunosorbent assay and the protein expression of aromatase,IL6-receptorα(IL6-Rα),TNF-receptor 1(TNF-R1)of the adipose issues were measured using the Western blotting.Result All the measurements of group FO were significantly higher than group N,except the serum testosterone.After 8 weeks of aerobic exercise,the body weight of group FE was significantly lower than that of group FO,while the average level of the testosterone,estradiol,IL6,TNFαand serum estradiol,and the expressions of adipose tissue aromatase and TNF-R1 protein were lower than group FO(P<0.05).Moreover,the intake of food,calories,abdominal fat weight and body fat percentage of group FE were lower than group FO(P<0.01).After 8 weeks of dietary intervention,the Lee’s index,serum estradiol and TNF-R1 protein expression in the adipose tissue,as well as the body weight,food intake,calorie intake,abdominal fat weight,body fat percentage,adipose tissue testosterone,estradiol,IL6 and TNFαof group FN were lower than group FO.Conclusion Obesity induced by the high-fat diet can increase the expression of inflammatory cytokines and aromatase in the adipose tissue of male mice,and further increase the level of estrogen in the body.The aerobic exercise may reduce the expression of aromatase in adipose tissue of male obese mice mainly through the TNFα-TNFR1 pathway,and contribute to the restoration of balance in the aromatation of androgens in adipose tissue.The intervention of the lipid-lowering diet may not mainly affect the sex hormone levels of male obese mice through the adipose tissue inflammation-aromatase pathway.