The Effects Of Intrauterine And Postnatal Nutritional Changes On The Cardiovascular System And Liver Of Offspring

Background: Obesity is caused by the long-term imbalance of energy intake and energy consumption,and the obesity during the period of pregnancy and lactation may have many adverse effects on the offspring,for example,the increased incidence of high blood pressure,high blood sugar,reduced insulin sensitivity,obesity,fatty liver diseases and tumor at the adulthood of the offspring.However,the effects of perinatal obesity during perinatal period on the cardiovascular system of offspring remain poorly understood and need to be further studied.In addition,neonatal overeating is related to obesity and insulin resistance in adulthood,and its effects on the liver need further study.Therefore,in this study,ICR mice were put into high fat diet and then bred with healthy male mice to generate offspring from high fat diet moms(HFD-O)and a control offspring born from low fat diet mothers(LFD-O),to explore whether perinatal obesity during pregnancy and lactation had an effect on the cardiovascular system of the offspring.Secondly,to investigate whether obesity in early life due to neonatal overeating has impact on the development of non-alcoholic steatohepatitis(NASH),a neonatal overfeeding through litter size reduction(Small litter size,SL)postpartum and subsequent methionine and choline-deficient(MCD)diet feeding as young adult were used in the current study.Methods: First of all,the female ICR mice(6-8 weeks of age)were selected and randomly divided into high fat diet group(HFD)and low fat diet group(LFD).Under the free drinking and feeding conditions,high fat diet mice were fed with HFD,and low fat diet mice were fed with LFD to establish HFD induced obese model.Then these mice were bred with normal young male mice.The success of conception was examined by vaginal smears.The birth weight and body weight of the offspring from HFD mothers(HFD-O)and LFD mothers(LFD-O)were carefully recorded.At postnatal day 21,all offspring mice were switched to solid standard diets and separated male from female.As adult(25 weeks of age)blood pressure was monitored.The HFD-O and LFD-O were killed,and the thoracic aorta and heart and other visceral tissues were collected,followed by HE staining to observe the thickness of the vessel wall and the morphology of the heart and other tissues.The neonatal overeating mice were produced based on our previous reports.At postnatal day 1,litter size was adjusted into either 3pups/litter(small litter size,SL)or 10pups/litter(normal litter size,NL).At postnatal day 21,SL and NL mice were switched to standard solid diet.At the age of 11 weeks,SL and NL mice were fed with methionine choline deficiency(MCD)diet and standard food(S)for anther 4 weeks respectively.Hematoxylin eosin staining,oil red O staining,F4/80 immunohistochemical staining,quantitative reverse transcription polymerase chain reaction(RT-PCR)and Western blotting method were performed.Result: After high fat diet(HFD),the body weight was significantly higher than that in the low fat diet(LFD)group,and the weight of the offspring of the offspring was significantly higher than that of the female offspring of the mother generation(LFD).After the blood pressure monitoring of the offspring of the offspring,the blood pressure of the female offspring(HFD-O)of the mother generation high fat diet was higher than that of the female offspring(LFD-O)of the mother generation low fat diet,and the morphological changes of the heart were also changed.Compared with NL mice,the weight gain of SL mice continued to increase for 2 weeks after adulthood,and glucose intolerance was more serious in adult rats.The mRNA expression level of Srebp-1c and Fasn in liver of 3-week old SL mice also increased.The MCD diet caused typical NASH,especially in SL-MCD mice.The fatty accumulation of the liver,large vascular lesions,balloon like lesions,inflammatory cell infiltration and the up regulation of the expression of TNF-α in the liver alpha mRNA,and the increase of ALT and AST in the serum levels proved fatty degeneration,and there was no significant difference in liver fibrosis in each group.SL-MCD diet had a certain effect on NASH.Conclusions: The results of this study reveal that maternal perinatal obesity has a certain effect on the cardiovascular system of offspring,and its specific mechanism needs further research and exploration.It is also shown that excessive eating and MCD diet induced in early life have an additive effect on metabolic function and the development of NASH in mice,which may lead to lipid metabolism disorder,which may lead to the accumulation of liver cells and the aggravation of liver inflammation.