Effects Of High Fat Diet On Learning And Memory And Hippocampal Neurogenesis Of Obesity-prone And Obesity-resistant Rats

ObjectiveTo observe the effect of high-fat diet on spatial learning and memory and hippocampal neurogenesis of obesity-prone and obesity-resistant rats, in order to provide experimental basis for nutrition intervention to improve cognitive function.Methods70 healthy male SD rats were randomly divided into two groups: basic feed control group(C group, n = 20) and high-fat diet group(HF group, n = 50), CF group would not be done any processing, HF group were fed with high fat diet for 8 weeks,then were divided into two groups according to the weight, respectively obesity-prone group(OP group, n = 10) and obesity-resistant group(OR group, n =9), continued original feeding, after 8 weeks, the effect of high-fat diet on learning and memory ability of rats was detected using Morris water maze test, the explore behavior and mood changes of rats were evaluated using Open field experiment and O maze experiment. Kept 12 hour fasting, the rats were made an anesthesia, body composition was measured using dual-energy X-ray bone density measurement.Then the rats were killed, the serm was collected, blood glucose and blood lipid of four were tested by automatic biochemical analyzer. The rats were perfused and fixed, brain tissue was collected, after fixed, dehydrated, embeded, sliced.Finally, immunofluorescence staining were taken to detect hippocampal neurogenesis and the expression of hippocampal GFAP and VEGF of rats.Results1.The effects of high fat diet on body weight, energy intake, body composition,glucose and blood lipid of four of rats At 8 weeks, body weight of OP group rats was significantly higher than that of C group and OR group, and this trend continued to the end of the experiment. Except the 9th and 10 th weeks, body weight of OR group rats was significantly higher than that of C group. Energy intake of all the groups had no significant differences(P >0.05).Compared with C group, the amount of fat tissue of OP group rats had a significantly increase(P<0.01), OR group also had a significant increase(P<0.01),but the increase is smaller than that of OP group. The amount of muscle tissue and bone mineral density of all groups did not have significant differences(P>0.05).Blood glucose and triglyceride levels of OP group rats were significantly higher than these of C group and OR group(P<0.01), the other three indicators had a rising trend but there were no significant differences(P > 0.05). Glucose and blood lipid of four of OP group rats were significantly higher than these of OR group. Except the low density lipoprotein, the other indexes of OR group were significantly lower than these of C group(P<0.05), other indexes did not exist significant differences.2. Effect of high fat diet on spatial learning and memory of rats Escape latency period of all the groups decreased significantly compared with the day before in Morris water maze experiment(P<0.05), on the 1st and 2nd day, the escape latent period of OP group is longer than that of OR and C group(P<0.05), the3 rd day, escape latent period of all the groups did not have significant differences(P>0.05). Platform quadrant stay time of all the three groups did not have significant differences.The time of staying in the platform quadrant and times of through the platform of all the groups did not have significant differences, but times of through the platform of OP group rats had a tendency to reduce. In O maze experiment, the times of entering into the interval and time of staying in the open interval had no significant differences of all the groups(P > 0.05). In open field experiment, all the indexes of total movement distance, the number of across the grid, the residence time and the central grid movement distance did not have significant differences(P>0.05).3. Effect of high fat diet on rat hippocampal neurogenesis Compared with C group, the hippocampal neurogenesis of OP group rats decreased significantly(P < 0.01), but OR group rats did not appear significant change(P > 0.05); Hippocampal neurogenesis of OR group was significantly higher than that of OP group(P<0.01).4.Effects of high fat diet on the expression of rats hippocampal GFAP and VEGF Compared with group C, the hippocampal GFAP positive area and the integral optical density of OP group rats were significantly increased(P < 0.01), while the hippocampal GFAP positive area and the integral optical density of OR group rats were not seen significant change(P>0.05). Hippocampal GFAP positive area and the integral optical density of OR groups rats were significantly lower than these of OP group rats(P<0.01).Compared with group C, the hippocampal VEGF positive area and the integral optical density of OP and OR group rats both were significantly decreased(P<0.01).Compared with OP group, hippocampal GFAP positive area and the integral optical density of OR group rats were not seen significant change(P>0.05).Conclusion1. High fat diet can lead to glucolipid metabolism disorder of obesity-prone rats, but the obesity-resistant rats did not appear the glucolipid metabolism abnormalities.2. High fat diet can damage the spatial learning ability of obesity-prone rat, but did not change the anxiety of the rats.3. High fat diet can reduce the hippocampal neurogenesis level of obesity-prone rats,but did not change the hippocampal neurogenesis level of obesity-resistant rats.4. High fat diet can reduce the hippocampal VEGF expression of the obesity-prone rats and increase GFAP expression. For obesity-resistant individuals, high fat diet did not increase the expression of GFAP, but reduced the expression of hippocampal VEGF.