Comparative Study Of HIIT On β₃ Adrenergic Receptor Effects In Visceral Adipose Tissue Of Obesity Prone/Resistant Rats

Objective:Obesity has become a major health threat in modern society.Excessive accumulation of visceral fat is more likely to lead to various metabolic diseases.High Intensity Interval Training（HIIT）has been shown to be effective in reducing body fat percentage,but its effectiveness in reducing visceral fat remains controversial.In addition to the exercise intensity,exercise time and other factors of HIIT program,subjects with different susceptibility to obesity are the important factors affecting HIIT fat reduction effect.The aim of this study was to compare the difference of visceral fat reduction in obesity prone（OP）and obesity resistant（OR）rats under the same HIIT intervention,and to explore the role ofβ₃AR-HSL,a key pathway of fat mobilization.Methods:Forty-eight male SD rats aged 7 weeks were placed in the upper quarter（12rats）as obesity-prone（OP）rats and the lower quarter（12 rats）as obesity-resistant（OR）rats in order of weight gain after 6 weeks of high fat diet feeding.They were further randomly divided into quiet feeding control group（D-OP and D-OR）and HIIT exercise intervention group（H-OP and H-OR）.The exercise group was given 12-week HIIT intervention(90～100%VO_2maxexercise for 1 minute at high intensity,and 50%VO_2maxexercise for 2 minutes at intermittent intensity.The running distance was matched with the moderate intensity exercise of 50%VO_2max for 45 minutes),and the control group was kept quietly.Body weight and food intake were observed during the intervention.After the intervention,the epididymal fat pad was taken and weighed.The area of epididymal fat cells was observed by HE staining,and the degree of liver fat infiltration was observed by oil red O staining.The expression ofβ3AR receptor,lipolysis rate-limiting enzyme HSL and phosphorylation on adipocyte membrane were observed by Western Blot.Results:（1）During the 6-week modeling period,the weight increase trend of the two groups was stable,and the weight of the OP group was always significantly higher than that of the OR group（P<0.05 or P<0.01）;During modeling,the intake of the OP group was significantly higher than that of the OR group（P<0.05）.（2）Repeated measure ANOVA showed that there was a significant interaction effect between"exercise"and"time"in OP（D-OP and H-OP）and OR（D-OR and H-OR）rats during the 12-week exercise intervention（P<0.01）,suggesting that HIIT intervention can inhibit the weight gain of OP and OR rats;Under the condition of quiet feeding,"obesity susceptibility"（OP and OR）and"time"had a very significant interaction effect（P<0.01）,the weight difference between OP and OR gradually increased,while HIIT intervention had no significant interaction effect on"time"and"obesity susceptibility"（OP and OR）（P=0.089）,suggesting that HIIT intervention could alleviate the weight difference between OP and OR.（3）Two-way ANOVA showed that"exercise"had no significant main effect on total food intake during the 12-week intervention period（P>0.05）,"obesity susceptibility"had a major effect（P<0.01）,but there was no interaction effect between the two factors（P=0.62）.The food intake of OP rats was higher than that of OR rats,and exercise had no effect on the food intake of the two phenotypes of rats.（4）The main effects of both"exercise"and"obesity susceptibility"on the body weight of rats after 12 weeks of intervention were very significant（P<0.01）,but there was no interaction between the two factors（P=0.33）.The weight of OP rats was higher than that of OR rats,and HIIT had no difference in inhibiting weight gain between the two types of rats.（5）The main effects of both"exercise"and"obesity susceptibility"on epididymal fat mass of rats were very significant,and there was an interactive effect（P<0.01）.The amount of epididymal fat in OP rats was significantly higher than that in OR rats（P<0.01）,HIIT intervention could significantly reduce epididymal fat mass in OP and OR rats（P<0.01）,HIIT had a more obvious effect on reducing epididymal fat volume in OP rats compared with OR rats.（6）The main effects of both"exercise"and"obesity susceptibility"on the area of adipocytes in epididymis of rats were very significant,and there was an interactive effect（P<0.01）,the area of epididymal adipocytes in OP rats was significantly larger than that in OR rats（P<0.01）,HIIT could significantly reduce the area of epididymal adipocytes in OP and OR rats（P<0.01）,HIIT reduced epididymal adipocyte area in OP rats more obviously than that in OR rats.（7）The main effects of both"exercise"and"obesity susceptibility"on the degree of liver fat infiltration of rats were very significant,and there was an interactive effect（P<0.01）.Liver fat infiltration of OP rats was significantly higher than that of OR rats（P<0.01）.Compared with OR rats,HIIT had a better effect on reducing the degree of liver fat infiltration in OP rats.（8）The main effect of"exercise"onβ₃AR expression in rat epididymal adipose tissue was very significant（P<0.01）,"obesity susceptibility"had no main effect（P=0.32）,but there was an interactive effect between the two factors（P<0.05）,the expression ofβ₃AR in epididymal adipose tissue of OP rats was significantly lower than that of OR rats（P<0.05）,HIIT significantly increased the expression ofβ₃AR in epididymal adipose tissue of OP rats compared with OR rats.（9）Neither"exercise"nor"obesity susceptibility"had a major effect on HSL expression in rat epididymal adipose tissue,and there was no interaction effect（P>0.05）,HIIT intervention had no effect on the expression of HSL in epididymal fat of OP and OR rats.The main effects of both"exercise"and"obesity susceptibility"on HSL-ser660 in rat epididymal adipose tissue were very significant（P<0.01）,but there was no interaction effect between the two factors（P=0.30）.HIIT intervention could increase HSL-ser660 protein expression in visceral fat of the two types of rats,but there was no difference in the effect of HIIT intervention on rats with different obesity susceptibility levels（OP and OR）.Conclusion:Under the same HIIT intervention,obesity prone rats lost more visceral fat than obesity resistant rats,the mechanism of which was related to HIIT enhancing the adiposis-related receptorβ₃AR in visceral adipose tissue of obesity prone rats.