Effects Of Wheel Running On Eating Behavior And Electrical Activity Of VTA-DA Neurons In Rats With High-fat Diet

Objective:The purpose of this study was to explore the neurobiological mechanism of the prevention and treatment of obesity from the perspective of exercise regulating food reward by observing the changes of eating behavior,the electrical activity of VTA-DA neurous,the rate-limiting enzyme TH of DA synthesis and the expression of glutamatergic neuron receptor in rats with high-fat diet after 4 weeks of voluntary wheel running.Method:Thirty 4-week-old female SD rats were randomly divided into high-fat diet control group?HCG,n=15?and high-fat diet exercise group?HEG,n=15?after adaptive feeding for 3 days.The rats were fed with high-fat diet and chow diet for 12 weeeks.HEG rats exercised independently with wheel for 12 hours a day for 5 days a week for 4 weeks from the9^th week.At the end of the experiment,body weight,Lee's index,weight of visceral fat?epididymal and perirenal fat?and eating behavior were measured,the preference of different foods was tested by conditioned place preference test?CPP?and double bottle test,and serum leptin level was measured by ELISA method.Western blotting was used to detect the expression of TH,NR1 and NR2B in midbrain,and localized expression of TH and NR1proteins in VTA of the rats was detected by double immunofluorescence labeling.The changes of electrical activity of VTA-DA neurons in different states were recorded by multi-channel electrophysiological technique in vivo.Result:?1?The body weight of HEG rats was significantly lower than that of HCG rats?P<0.01?,the Lee's index of HEG rats was significantly lower than that of HCG rats?P<0.01?,and the percentage of body fat of HEG rats was significantly lower than that of HCG rats?P<0.01?after 4 weeks of voluntary wheel running.?2?There was no significant difference in food intake between HCG and HEG rats,but the high fat diet preference and milk preference in HEG rats were significantly lower than those in HCG rats?P<0.01,P<0.01?,and in milk-induced conditioned place preference test,HEG rats were significantly lower than HCG rats?P<0.05?after 4 weeks of voluntary wheel running.?3?After 4 weeks of voluntary wheel running,the discharge frequency of VTA-DA neurons in HEG rats was significantly lower than that in HCG rats?P<0.05?,the discharge frequency of VTA-DA neurons in HEG rats was significantly lower than that in HCG rats after intraperitoneal injection of leptin?P<0.01?,and the change rate of discharge frequency of VTA-DA neurons in HEG rats was significantly higher than that in HEG rats?P<0.01?after injection of leptin.?4?After 4 weeks of voluntary wheel running,the level of serum leptin in HEG rats was significantly lower than that in HCG rats?P<0.05?,the expression of TH protein in mesencephalon of HEG rats was significantly higher than that of HCG rats?P<0.01?,and the expression of NR1 protein decreased significantly?P<0.01?,but there was no significant difference in the expression of NR2B protein?P>0.05?.Conclusion:Voluntary wheel running can improve the sensitivity of leptin in rats with high-fat diet,thereby regulating DA neuron plasticity to improve food reward,reducing their preference for high-fat diets,and ultimately improving body composition to delay weight gain.The decrease of glutamic acid NMDA receptor functional subunit NR1 is one of the mechanisms of exercise-mediated leptin to regulate the activity of VTA-DA neurons and improve food reward function in high-fat diet rats.