低温运动干预肥胖大鼠的脂肪组织类型及功能改变

Exercises under cold exposure change fat type and function in obese rats

背景:低温和运动干预下脂肪组织及其分布会产生变化,使脂肪组织功能发生改变,这对肥胖及相关代谢性疾病的治疗具有积极意义,但至今对不同低温暴露下运动的效应尚未报道,有待进一步研究。目的:观察5周不同方式低温运动干预后肥胖大鼠白色脂肪棕色化效应及解偶联蛋白1表达的变化。方法:将采用高脂饲料饮食方法建立的64只营养性肥胖SD大鼠随机均分为常温组、间歇低温组、急性低温组及持续低温组,其中每组又分别分为安静组及运动组。常温环境为24-26℃,低温环境为3-4℃,相对湿度均为50%-60%;持续低温每天均在低温环境中,间歇低温每天在低温环境4 h,急性低温在干预最后一天在低温环境暴露4 h;安静组自由活动,运动组隔天进行每次30 min共1 h的间歇跑台运动,跑速为25 m/min,坡度0°。5周后采用Micro-CT LCT200测量脂肪组织比率;采集肩胛间及腹股沟脂肪组织用苏木精-伊红染色观察其形态学变化;采用Western-blot检测腹股沟脂肪组织中解偶联蛋白1表达。结果与结论:①间歇低温运动组、持续低温安静及运动组肩胛间脂肪细胞体积显著减小,数量明显增多,脂滴逐渐消失,细胞间毛细血管逐渐增多;间歇及持续低温运动组大鼠腹股沟白色脂肪细胞中出现多室,细胞体积变小且均匀,组织更加紧密,具有明显的棕色化趋势;②持续低温运动组大鼠内脏脂肪率和体脂率最低,且显著低于常温安静及运动组、急性低温安静及运动组、间歇及持续低温安静组(P<0.05);③安静组中常温组的皮下脂肪率显著低于急性及间歇低温组(P<0.05),而运动组中急性低温组显著低于常温组(P<0.05);④3个低温安静及持续低温运动组棕色脂肪率均显著高于常温安静组(P<0.05),急性低温安静组显著高于急性低温运动组(P<0.05),间歇低温安静组显著高于间歇低温运动组(P<0.05),急性低温运动组显著低于间歇和持续低温运动组(P<0.05);⑤解偶联蛋白1表达方面,各运动组较其对应的安静组均显著上调(P<0.05),其中常温安静组最低,持续低温运动组蛋白表达最高,其次为间歇低温运动组(P<0.05);⑥结果显示,持续和间歇低温运动更能诱导皮下腹股沟白色脂肪棕色化,降低肥胖机体的体脂率,该效应与腹股沟脂肪组织形态学及解偶联蛋白1变化有关。

BACKGROUND:Cold exposure and exercise serve as two powerful physiological stimuli to change the type and function of fat,which has positive implications for the treatment of obesity and related metabolic diseases.So far,it remains to be unclear whether exercise in the different cold exposure can produce an addictive effect on fat change.OBJECTIVE:To observe the browning effect of white fat and the expression of uncoupling protein 1 in obese rats after 5 weeks of exercise intervention under cold exposure.METHODS:Sixty-four Sprague-Dawley rats were selected to establish animal models of nutritional obesity.They were randomly divided into four groups:normal control group(NTS),normal exercise group(NTE),acute cold control group(ACS),acute cold exercise group(ACE),intermittent cold control group(ICS)and intermittent cold exercise group(ICE),continuous cold control group(CES),and continuous cold exercise group(CEE).The normal temperature environment was 24-26℃,the cold environment was 3-4℃,and the relative humidity was 50%-60%.For acute cold exposure,the rats were exposed to low temperature for only 4 hours before the end of the experiment;for intermittent cold exposure,the rats were exposed to low temperature for 4 hours per day;for continuous cold exposure,the rats stayed in a cold environment all day.The protocol for treadmill running in exercise groups was as follows:25 m/min(speed),0℃(slope),30 minutes once,for two sections.Sampling was conducted after 5 weeks.The fat rate was measured by Micro-CT LCT200.The interscapular and inguinal fats were collected for hematoxylin-eosin staining to observe morphological changes,and the expression of uncoupling protein 1 in the inguinal fat was examined by western blot.RESULTS AND CONCLUSION:In the CES,ICE and CEE groups,the volume of interscapular fat cells decreased significantly and the cell number increased significantly;the lipid droplets gradually disappeared and the intercellular capillaries gradually increased.The white fat cells in the inguinal of the rats in the ICE and SEE groups were multilocular,with smaller and more uniform cell size and tighter tissue,showing an obvious browning trend.Compared with the CEE group,the visceral and body fat rate were significantly declined in the NTS,NTE,ACS,ACE,ICS and CES groups(P<0.05).The subcutaneous fat rate of the NTS group was significantly declined compared with that of the ACS and ICS groups(P<0.05),and that of the ACE group was significantly declined compared with that of the NTE group(P<0.05).Compared with the NTS group,the brown fat rate was significantly higher in the ACS,ICS,CES and CEE groups(P<0.05);compared with the ACE group,the brown fat rate was significantly higher in ACS group(P<0.05);compared with the ICE group,the brown fat rate was significantly higher in ICS group(P<0.05);compared with the ACE group,the brown fat rate was significantly declined in ICE and CEE groups(P<0.05).The expression of uncoupling protein 1 in each exercise group was significantly up-regulated compared with the corresponding control group(P<0.05).The expression of uncoupling protein 1 was lowest in the NTS group,and highest in CCE group,followed by the ICE group(P<0.05).To conclude,exercises under continuous and intermittent cold exposure can induce the browning of subcutaneous inguinal white fat and reduce the body fat rate of obese body,which may be correlated with the morphological changes of inguinal fat as well as the changes of uncoupling protein 1.