| ?Background?The "Developmental Origins of Health and Disease Hypothesis(DOHa D)" theory suggests that a poor intrauterine environment may affect the metabolic pattern,growth and development of the fetus and increase the adulthood of chronic diseases such as obesity,cardiovascular disease and diabetes,etc.Pregnancy is a complex metabolic state.As the pregnancy progresses,a series of changes will occur in the metabolism of pregnant women.During pregnancy,the placenta secretes a series of peptide hormones,growth factors,and cytokines to regulate maternal metabolism and fetal growth.These hormones work together to cause peripheral insulin resistance.If the mother is obese or has limited insulin secretion,it will not be able to compensate for this physiological change,which will eventually lead to metabolic disorders during pregnancy,which in turn will have a serious impact on the long-term health of the mother and offspring.Exercise is one of the important aspects of maintaining a healthy lifestyle.Reasonable exercise is one of the main points of health promotion during pregnancy.Appropriate exercise is beneficial to improve insulin sensitivity,anti-oxidative stress and reduce inflammation.and it plays an important role in prevent and control metabolic diseases during pregnancy.More research in this field focuses on maternal exercise to improve insulin sensitivity during pregnancy,to control excessive growth of maternal body weight during pregnancy,or to improve and prevent pregnancy complications such as gestational diabetes or pre-eclampsia.There are still limited reports on the positive health benefits of maternal pregnancy during the birth and even long-term of the offspring,especially the study of maternal exercise during pregnancy to regulate the energy metabolism of pregnant mice and offspring.Although a few studies have examined the metabolic characterization of progeny,these studies have not thoroughly clarified the triggering mechanisms of these changes,and there are some uncertainties in the health links between prenatal physical activity and offspring.?Objective?1.Through the Forced swimming of obese pregnant mice induced by high-fat diet revealed the central and peripheral regulation mechanisms of pre-pregnancy and pregnancy exercise on maternal energy metabolism.2.To observe the effects of long-term exercise of maternal on obesity and metabolism in offspring,and to study whether there were gender differences in the metabolic effects of high fat and exercise intervention on offspring.3.In the case of different dietary structures of the offspring,it is necessary to explore whether the metabolic genetic effects of long-term high-fat and exercise intervention in the maternal are different.?Materials and Methods?Experiment 1:Three-week-old female C57BL/6 mice were randomly divided into 4 groups after weaning,Standard Chow Diet(SC),Standard Chow Die+Exercise(SC-Ex),and high-fat quiet group(High Fat Diet,HFD)and High Fat Diet+Exercise(HFD-Ex).After 13 weeks of forced swimming intervention,the male mice were co-caged with the same age,and the GTT and ITT tests were performed on the 14 th day of pregnancy.The energy metabolism test was performed during the 2-day on rest period.On the 19 th day of pregnancy,6 pregnant mice were taken euthanasia after component analysis,liver tissue was extracted for histopathological analysis.serum was analyzed for metabolic related factors.real-time quantitative PCR was used to measure the relative expression of POMC,NPY and Ag RP m RNA in hypothalamus.Immunoblot assay for LGR4,RSPO-1,PGC1?,PPAR?,PDK4,UCP2 protein expression in liver.Experiment 2: On the basis of the first part,we studied the offspring of the two high-fat groups.After the mother gave birth naturally,each litter was adjusted to 7 pups,and the HFD and HFD-Ex mother were fed a SC diet(12% fat supply).Young mice were weighed once a week until the end of 4 weeks of lactation.On the 28 th day,Take 1 mice in each nestto GTT and ITT tests.At the same time,each female and male mice in each nest were subjected to body composition analysis,followed by euthanasia and sampling.The mice were tested for diabetes 8 factor and IL-6 by suspension chip;TG,TC and FFA were determined by colorimetry.Experiment 3: Male offspring from HFD and HFD-Ex mice were randomly divided into two groups(8 x 2 groups)at the end of 4 weeks of lactation.A total of 16 mice were fed with high fat for 6 weeks.All the remaining offspring fed SCdiet to 52 weeks(1 year).HFD and SCfood are the same as the mothers.During the period of high-fat intervention,the weekly food intake is recorded,and the weekly energy intake is calculated.The GTT test is performed after 6 weeks of high-fat,the ITT test was conducted 3 days after the GTT test.The SC diet of offspring conducted GTT tests and ITT tests at weeks 8,12,24,36 and 52.The body composition analysis was performed at the 10 th week of the HFD and SC diet of offspring,52 nd week age in SC dietof offspring.In the SC diet intervention,the offspring was injected with insulin or normal saline 15 minutes before the injection,and the liver was subjected to Western blotting to analyze the level of p-Akt.The hypothalamic arcuate nucleus immunofluorescence analysis the expression of NPY.The remaining offspring were fed to 52 weeks,and the metabolic compartment was measured.Statistical methods: All experimental data were statistically processed using SPSS 19.0 software,and each data was expressed as mean ± standard error(Mean ± SEM).The first part of the maternal diet and exercise effects were analyzed by two-way ANOVA;The second and third part of the group were analyzed by independent sample T test,P<0.05 was defined as the boundary value of the difference significance level..?Results?1.With the development of pregnancy,the weight of the dams gradually increased.In the first 2 weeks of pregnancy,there was a significant difference in body weight between the groups.In the last 3 days of pregnancy,the body weights of the four groups were consistent,and there was no significant difference between the groups(P>0.05).2.Compared with the normal diet,after 15,30,60,and 120 minutes,the high-fat diet group resulted in a decrease in GTT,and the HFD-Ex group showed a significant improvement in glucose tolerance compared with the HFD group(P< 0.05);ITT test also showed consistent results.body composition analysis found no significant difference in total fat mass between the two groups(SC = 4.01 ± 0.6 g,SC-Ex = 3.60 ± 0.64 g,P > 0.05)The HFD-Ex group was significantly lower than the HFD group(HFD = 7.56 ± 1.59 g,HFD-Ex = 6.10 ± 1.41 g,n = 8-10,P< 0.05).3.The HFD group had the lowest fertility rate of only 44%,and exercise improved to some extent(60% in the HFD-Ex group),but still less than 76% in the general group.There was no significant difference between body weight and length in fetuses of 4 groups(P>0.05).At the same time,there was edema in both the fetus and the newborn mice in the HFD group compared with the SC group.4.Compared with the SC group,the HFD group had a significant increase in Cholesterol,FFA,Triglycerides,and HOMA-IR.There was no significant difference in the two SC groups,but in the HFD groups,this situation was significantly different,Compared with HFD,HFD-Ex showed significant improvement in each index(P< 0.05).5.Compared with the HFD group,HFD-Ex was significantly higher in locomotor activity,RQ(VCO2/VO2)and energy expenditure(P< 0.05),while there was no significant difference between SC-Ex and SC groups.Compared with SC group,The HFD group was significantly lower than the former at dark or during the light(P< 0.05).6.Compared with the HFD group,the expression of LGR4 and UCP2 in the HFD-Ex group was significantly decreased,while the expression of PGC1?,PDK4 and PPAR? was significantly increased(P<0.05).Compared with SC,there were no significant difference in SC-Ex,except for UCP2.7.Liver tissue HE and oil red O staining showed a large number of lipid droplets and fat vacuoles in the HFD group,and there was a local improvement in HFD-Ex.In the SC and SC-Ex groups,this situation was significantly improved,no The presence of vacuolar lipid droplets.PAS staining observed hepatic glycogen depletion,liver pathology of pregnant mice in the HFD group showed hepatic glycogen depletion,while the HFD-Ex group showed normal glycogen expression in addition to hepatic steatosis.8.Compared with the SC group,the expression of NPY m RNA in the HFD group was increased(P<0.05),while the expression of POMC m RNA was decreased(P<0.05).Compared with HFD,the expression of NPY m RNA in the HFD-Ex group was decreased(P<0.05),while the expression of POMC m RNA increased(P<0.05),and the POMC m RNA of SC-Ex group also increased significantly compared with SC group.9.Through the detection of IL-6,male offsprings have significant inter-group differences,while female offspring did not observe differences between each groups;blood lipid index TG also observed the male progeny from HFD-Ex were significantly lower than the progeny from the HFD group(P<0.05),while the difference was not significant in the female group;no difference was found between the remaining FFA and CH indicators.10.Among the Glucagon and GIP indicators,we observed a significant improvement in the HFD-Ex group compared to HFD in male mice,but no statistically significant differences were found in female mice.The HFD-Ex offspring was significantly improved Leptin compared with HFD in males and females offspring(P<0.05).The other indicators did not find differences between groups.11.Significant differences in body weight persisted in the two groups of offspring after the end of the lactation period.The AUC of the HFD group offspring was significantly higher than that of the HFD-Ex group,P<0.05.After 6 weeks of high fat,there was no significant difference in body composition between the two groups.In the case of SC feeding,at the 10 th week and the 52 nd week,the body composition of the HFD-Ex group was significantly lower than that of the HFD group.P< 0.05.In the first two weeks of the offspring high-fat diet,the energy intake of the HFD group was significantly higher than that of HFD-Ex matemal,but at the third week of high-fat(7 weeks),the energy intake of the HFD-Ex group was higher than the control group,and in the following weeks,the energy intake between the two groups did not show differences.12.In the case of general diet,the GTT and ITT trials were performed on the offspring of the two groups at weeks 8,12,24,36,and 52.There was a significant difference in glucose metabolism between the two groups.AUC gradually increased with the increase of the age of the offspring,and there was a difference between the groups after 24 weeks.The offspring in the HFD group were significantly higher than the HFD-Ex group.At week 52,the body weight of the HFD-Ex group was significantly lower than that of the HFD group,P < 0.05.13.Compared with the HFD group,the NPY expression of the HFD-Ex group was significantly lower in offspring(P<0.05).In addition,it was found by Western blotting that there was no significant difference in the expression of Akt(Ser473)phosphorylated protein in insulin(-),but there was an inter-group difference in insulin(+),P<0.05.14.At week 52,the results of TSE showed that activity was no significant difference between the two groups during light,and at dark(18:00-6:00),the offspring of the HFD-Ex group were significantly higher than HFD group.In the energy consumption,the difference between the groups existed both day and night,and the offspring of the HFD-Ex group were significantly higher than the HFD group.In addition,on the RQ index,we did not find significant differences between groups.?Conclusion?1.Long-term pre-pregnancy and pregnancy swimming can effectively improve the peripheral and central regulation mechanisms of energy metabolism during maternal pregnancy,but can not completely reverse the adverse metabolic effects of long-term high-fat diet.2.The metabolic inheritance of the offspring has a certain gender bias,and the metabolism of the mother can make the male offspring genetically susceptible 3.Maternal movement can effectively improve the ability of glycolipids metabolize in childhood of offspring.4.In the SC diet mode,long-term exercise in the mother can reverse and counteract the permanent metabolic risk of high-fat exposure in the early life of the offspring.5.In the HFD diet mode,the high-fat feeding memory from mother may be “awakened”,and the metabolic protective effect obtained by long-term exerciset with mother may also gradually weaken with the prolongation of high-fat diet exposure time. |
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