| As the rapid development of modern society and the improvement of people’s living standard,people eat a lot of junk food with high energy and low nutrition which lead to the increasing odds of obesity.Obesity is a kind of disease which is harmful to our body,because of the energy metabolism imbalance and more calorie intake than consumption.It leads to weight gain with the combination of inheritance and environment.Obesity has become a problem worldwide.Rapid increases of obesity are occurring in many countries.In the US,data from latest National Health and Nutrition Examination Survey(compiled from 1999-2010)indicates that 69%of adults are overweight or obese.This increased risk of obesity is thought to be due to hyperphagia and decreased physical activity.A lot of data show that obesity not only threatens the health of human being,but also takes immeasurable damage to the next generation at the same time.The majority of infants born in the United States and other western countries are exposed to maternal obese or overweight metabolic status and high fat diet(HFD)consumption during perinatal development.With the improvement of modern society,people gradually realize the influence of parental obesity on the next generation which promote them to pay more attention to their health.At present,there are plenty of researches about maternal high fat diet.By contrast,few is about paternal high fat diet.The purpose of this experiment is not only to study the effect of high fat diet on animals themselves but also to investigate the relationship between paternal high fat diet and offspring.Obesity is not only one of the metabolic diseases,but also one of the most important risk factors for diseases such as hypertension,diabetes,cardiovascular disease,stroke and mental disorders.A great number of studies have shown that the prevention of obesity can reduce the occurrence of chronic diseases both at home and abroad.High-fat diet(HFD)have been used for many years to study the effects of increased adiposity,dyslipidemia and insulin resistance in rodents.It has been shown that the disturbances originated by high-fat feeding closely resemble the metabolic disturbances observed in humans.A great amount of data showed that high fat diet and obesity are corelated with the dysfunction of the central nervous system.Studies have shown that high fat diet can induce neural inflammation and synaptic damage,resulting in neurodegeneration and cognitive impairment.Considerable clinical evidence suggested that HFD consumption and the presence of metabolic dysfunction were sufficient to exacerbate brain aging,promoting the development of cognitive alterations including dementia.Some studies demonstrated that HFDs were able to increase amyloid beta peptide(Aβ)levels and Aβ-neuropathy in brains of mice exhibiting Alzheimer’s disease(AD)pathology.Experimental evidence suggested that alterations in insulin metabolism may influence the onset of AD through their influence on the synthesis and degradation of amyloid beta peptide(AP).Researchers showed that the mice after 18 weeks’ high fat diet displayed significantly decreased spatial learning and memory compared with the control group in the water maze test.In addition to the damage of rodents’ learning and memory,high fat diet is also closely related to depression.The one who is overweight or obesity is more likely to have depression.Recent studies showed that after 9 weeks’ high fat diet,the rats displayed depression-like behavior in the sucrose preference test.The other researcher gave the mice 12 weeks’high fat diet(fat provides 58%calories)and the high fat diet group have shown increased immobility time compared to the control group in the forced swimming test.In exploring the connection between high fat diet and anxiety,the data showed that the high fat diet was inversely related to anxiety.Prasad gave rats 1 week high fat diet(fat provide 90%calories),the rats displayed anxiolytic behavior.Cryan gave the 3 weeks’ old mice 12 weeks high fat diet(fat provide 45%calories),and then gave them chronic social defeat stress.The high fat diet mice showed anxiolytic behavior in the light dark test.By contrast,some experts presented different ideas.They gave rats 8 weeks’ high fat diet(fat provides 35%calories)and the rats showed anxiety-like behavior.Sharma gave 2 months’ old mice 12 weeks’ high fat diet(fat provide 58%calories)and the mice displayed anxiogenic behavior in elevated plus maze and open field test.The different composition and sources as well as the duration of high fat diet can cause various results.Based on the above results,we’d like to deeply study the connection between different duration of high fat diet and anxiety.In recent years,scientists set up the model through giving rodents high fat diet.In order to investigate the relationship between high fat diet and anxiety,we designed the following experiments.We chose 3 weeks’ old C57/B6J male mice.After 1 week adaptation,they were randomly grouped with the control group and the high fat diet group.The data showed that the weight and energy accumulation of high fat diet group increased remarkably compared with the control group after 2 months’ high fat diet.We had also tested the insulin levels and fasting plasma glucose.The data showed that the insulin levels and fasting plasma glucose of the high fat diet group were significantly higher than the control.The high fat diet group had reached the standard of diabetes.Then we tested the high fat diet mice in the behavior tests.We used the open field test,elevated plus maze and light dark test for anxiety tests.The elevated plus maze showed that the time spent on open arms of the high fat diet mice was significantly longer than the control.The light dark test showed that the high fat diet mice preferred to stay in the light part compared with the control group.All the anxiety behavior tests showed that the high fat diet mice displayed anxiolytic behavior compared with the controls.It indicated that high fat diet was related with anxiolytic behavior.In order to explore whether the high fat diet mice displayed depression-like or anti-depression like behavior when they already had anxiolytic behavior,we designed the forced swimming test.The results showed that the immobility time between the high fat diet mice and the control mice displayed no difference.It indicated that 2 months’ high-fat diet mice didn’t show any depression-like behavior when they already had diabetes.And the high fat diet may not be involved in the regulation of depression behavior.In order to test if the high fat diet took part in the regulation of learning and memory,we designed the following experiment.We tested cued and contextual fear conditioning.In fear conditioning test,there was no significantly difference in immobility time between the high fat diet group and control group.It indicated that the 2 months’ high fat diet didn’t have any impact on their learning and memory.In order to explore the effect on the offspring from paternal high fat diet,we designed the following experiments with the 2 months’ high fat diet mice mating with the same age females.The females were fed with normal diet.Then we got the offspring who were fed with normal diet.When they were 2 months’ old,we used the open field test,elevated plus maze and light dark test for anxiety tests.The elevated plus maze showed that the time spent on open arms of the offspring of paternal high fat diet was significantly longer than the one whose father were fed with normal diet.The light dark test showed that the entries of the offspring of paternal high fat diet group were significantly more than the control groups.The tests showed that the male offspring of paternal high fat diet group displayed anxiolytic behavior compared with the controls.It indicated that offspring whose father were fed with high fat diet displayed with anxiolytic behavior.Furthermore,we also wanted to know if the paternal high fat diet had any effects on offspring about depression like behavior and learning and memory.Then we designed the forced swimming test and fear conditioning.The results showed that the immobility time between the offspring of paternal high fat diet mice and the control mice displayed no difference.It indicated that the offspring of paternal 2 months’high fat diet didn’t show any depression-like behavior.And the paternal high fat diet may not be involved in the regulation of depression behavior in our experiment.In order to test if the paternal high fat diet took part in the regulation of learning and memory of the offspring,we designed the following experiment.We tested cued and contextual fear conditioning.On dayl,we tested the mice for three trails.On day2,mice were taken to face the same condition to test the contextual freezing.The results showed that the offspring of the high fat diet group had the trend that the freezing of offspring of the high fat diet group is lower than the controls.But it didn’t yet reach a statistically significance.It indicated that the paternal high fat diet may influence the offspring’s learning and memory.And we need to expand the sample size to further repeat this experiment.In order to deeply study the mechanism between anxiety and high fat diet,we had designed the following experiments.The cerebrum was quickly isolated.The protein expression in the middle of the prefrontal cortex,the hippocampus and amygdala were tested by western blot.It was widely accepted that the anxiety disorder may be related to the dysregulation of neurotransmitter such as GABA,5-HT and NE.Selective serotonin reuptake inhibitors(SSRIs)are used as antidepressants in the treatment of major depressive disorder and anxiety disorders.The knock out of 5-HT1A receptor and the stress-inducing release of NE can increase the anxiety behavior.Monoamine oxidase A is an enzyme of monoamine oxidase.It preferentially deaminates norepinephrine,epinephrine,serotonin and dopamine.5-HT is metabolized mainly to 5-HIAA.As we all know,the high fat diet group displayed anxiolytic behavior compared with the controls after 2 months’ high fat diet.We wanted to know if the expression of MAOA changed and if MAOA participated in the regulation of anxiolytic behavior.We selected three brain regions which were the middle of the prefrontal cortex,the hippocampus and amygdala to detect the protein expression of MAOA.The results showed that the expression of MAOA of the high fat diet group in amygdala decreased significantly compared with the control group.,While there was no difference in the middle of the prefrontal cortex or the hippocampus.These results indicated that MAOA was down-regulated in the amygdala.Whether the down-regulation of MAOA is the mechanism that the high fat diet causes anxiolytic behavior deserves further investigation.In order to investigate the relationship between the different duration of high fat diet and anxiety,we studied different time points of high fat diet.We gave 2 months’old mice 4 weeks’ and 12 weeks’ high fat diet respectively.And we used the open field test,elevated plus maze and light dark box for anxiety tests.The results showed the mice of 4 weeks’ high fat diet had already displayed anxiolytic behavior.While when the duration of high fat diet came to 12 weeks,the anxiolytic behavior disappeared..Sirtuinl(SIRT1),known as NAD-dependent deacetylase sirtuin-1,is a protein that in humans is encoded by theSIRT1 gene.In recent years,it showed that SIRT1 played an important role in cancer,neurodegenerative disease,cardiovascular disease,type 2 diabetes and lipid metabolic disorder.We found that the protein level of SIRT1 was decreased in high fat diet group after one month high fat diet.In order to explore the mechnism between anxiolytic behavior and SIRT1,we gave the mice intraperitoneal injection of SIRT1 activator.Then we found that the HFD+saline group showed the anxiolytic behavior compared with the CD+saline group.And the HFD+RSV group showed that the anxiolytic behavior disappeared.It indicated that SIRT1 might took part in the regulation of anxiolytic behavior.In conclusion,after 1 month’s high fat diet,the high fat diet mice displayed anxiolytic behavior.However,when the duration of high fat diet came to three months,the anxiolytic behavior disappeared.The protein level of SIRT1 of the high fat diet group was decreased after one month’s high fat diet.After the intraperitoneal injection of SIRT1 activator,the anxiolytic behavior disappeared.The offspring of paternal 2 months’ high fat diet also displayed anxiolytic behavior.MAOA was down-regulated in the amygdala after 2 months’ high fat diet.Whether the down-regulation of MAOA was the mechanism that the high fat diet caused anxiolytic behavior deserved further investigation.The reason why MAOA was down-regulated in the amygdala also needed further study. |
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