Effects Of Exercise And Diet Intervention On Metabolism And Leptin Sensitivity In Obese Mice

Objective:Obesity is caused by an imbalance between energy intake and energy expenditure.The hypothalamus is a key center for the regulation of the body’s energy balance.Depending on the nutritional and energy status of the human body,adipose tissue secretes leptin,which crosses the blood-brain barrier and binds to leptin receptors in neurons that regulate energy balance in the hypothalamus,thereby regulating nutritional status and energy balance.Studies have found that long-term high-fat diet can induce leptin resistance in the hypothalamus,resulting in a decrease in the sensitivity of the hypothalamus to leptin,imbalance in the energy balance regulation system,and ultimately lead to weight changes and obesity.The fundamental changes in the energy balance system make dieting to lose weight is easy to relapse.Therefore,controlling energy balance through lifestyle changes will be a never-ending task if only to lose weight without repairing the energy balance regulation system.Exercise plays a good role in improving hypothalamic leptin resistance and increasing leptin sensitivity.Increased leptin sensitivity means that the energy regulation system of the hypothalamus is repaired.Based on the above,in this study,by constructing a mouse model of exercise and diet intervention,the phenotype,metabolic indicators,leptin sensitivity and leptin receptor and other indicators of mice in each group were analyzed to explore the effect of exercise and diet intervention on the metabolism and leptin sensitivity of obese mice.Method:Fifty seven-week-old SPF grade C57BL/6 male mice were randomly divided into two groups and fed with low-fat diet（SD,n=12）and high-fat diet（n=38）,respectively.The mice that meet the obesity model conditions in the group were selected and randomly divided into four groups for different interventions:high-fat quiet group（HFD,n=8）,high-fat exercise group（HFD+E,n=8）,high-fat switch to normal diet quiet group（HFD→SD,n=5）,high-fat switch to normal diet exercise group（HFD→SD+E,n=8）.Mice in HFD+E group and HFD→SD+E group performed moderate-intensity（75%VO₂max）treadmill exercise for 16 weeks,5 days a week,1 hour a day.The mice in each group were weighed every 2 weeks since the modeling,and the body composition,serum leptin concentration,m RNA expression of hypothalamic leptin receptor,energy metabolism indexes,and leptin sensitivity were measured 1 week after the exercise intervention.Results:（1）Two-way analysis of variance showed that exercise had main effects on body weight,fat mass,fat percentage,brown fat mass,serum leptin concentration,and unit energy expenditure（p<0.05）.Diet had main effects on body weight,fat mass,fat percentage,brown fat mass,subcutaneous fat mass,epididymal fat mass,serum leptin concentration,respiratory quotient,non-exercise physical activity,basal metabolism,energy expenditure,energy intake,unit energy intake（p<0.01 or p<0.05）.Exercise*diet had an interaction effect on body weight,fat mass,serum leptin concentration,hypothalamic leptin receptor m RNA expression,non-exercise physical activity,energy expenditure,and unit energy expenditure.（2）Compared with SD group,HFD group’s body weight,,fat mass,and body fat percentage were significantly increased（p<0.01）;compared with HFD group,HFD+E,HFD→SD,HFD→SD+E group’s body weight,fat mass,and body fat percentage were significantly decreased（p<0.01）.（3）Compared with the SD group,the serum leptin concentration of HFD group’s was significantly increased（p<0.01）.Compared with the HFD group,the serum leptin concentration of HFD+E,HFD→SD,HFD→SD+E group was significantly decreased（p<0.01）.Compared with SD group,the m RNA expression level of hypothalamic leptin receptor in HFD group was significantly increased（p<0.01）;compared with HFD group,the m RNA expression level of hypothalamic leptin receptor in HFD→SD group was significantly decreased.（4）The results of H＆E staining and Oil Red O staining showed that compared with the SD group,the liver lipid accumulation in the HFD group was significantly increased,and the volume of epididymal adipocytes was significantly increased.Compared with the HFD group,the HFD→SD+E group and the HFD→SD group had significantly less lipid accumulation in the liver,and the volume of epididymal adipocytes was significantly reduced.（5）The results of energy metabolism indicators showed that compared with HFD→SD+E group,the energy intake and energy consumption of HFD→SD group were significantly lower（p<0.05）,which together indicated that the HFD→SD group may be in the obesity maintenance stage.Easier to regain weight.（6）The results of leptin sensitivity test showed that compared with intraperitoneal injection of PBS,there was no significant difference in energy consumption and intake of HFD and HFD→SD groups after intraperitoneal injection of leptin.Compared with intraperitoneal injection of PBS,after intraperitoneal injection of leptin,there was no significant difference in energy consumption among SD,HFD+E,and HFD→SD+E groups,but energy intake was significantly decreased（p<0.05）.The above indicated that leptin sensitivity was impaired in HFD group,not improved in HFD→SD group,and increased in HFD+E,HFD→SD+E group.Conclusion:Long-term high-fat diet disrupts energy balance regulation in mice,reduces hypothalamic leptin sensitivity,and induces leptin resistance.Single dietary intervention can reduce body weight,fat mass,body fat percentage,and serum leptin concentration in obese mice,but cannot improve leptin sensitivity.Aerobic exercise,aerobic exercise combined with diet control intervention can improve the metabolism and leptin sensitivity of obese mice,and the effect of combined intervention is better.