Study Of Prepregnancy Obesity Affects The Nutrition Of Long-Chain Polyunsaturated Fatty Acids In Fetal Mice

Objective: In this study,high-fat diet was used to establish model of pre-pregnancy obese mice.To explore how pre-pregnancy obesity affects the nutrition and related mechanisms of long-chain polyunsaturated fatty acids in fetal mice by observing the expression of liver desaturase in the mother mice,the development of placenta and the expression of placental fatty acid transporter.Methods: Four-week-old C57BL/6J mice were selected and fed with high-fat diet for one week after adaptive feeding.After 10 weeks,the high-fat diet-fed groups were divided into diet-induced obesity(DIO),diet-induced overweight(DIW),and diet-induced obesity resistance(DIR)groups according to the increase in body weight of the mice,and a normal feed-fed control group(CON)was also established.After the mouse were conceived,the high-fat group continued to feed the high-fat diet,and the control group continued to feed the normal diet,and the food intake of the mice in each group was recorded.The mouse were anesthetized on the 18 th day of pregnancy.The blood and liver of the mother mouse were taken,and the liver weight of the mother mouse was recorded.The fetal mouse and placenta were stripped and dried.The fetal mice body length and placental diameter were measured,and the fetal mice body weight and placental weight were weighed.Collected fetal blood.The blood was separated into plasma and red blood cells after centrifugation.qRT-PCR was used to detect mRNA expression of desaturases(FADS1,FADS2)in maternal liver tissues and mRNA expression levels of inflammatory factors IL-1?,TNF-? and placental transporters(CD36,FATP4 and FABPpm)in placental tissues.The expression levels of protein(FADS1,FADS2)in maternal liver tissue,inflammatory factors IL-1?/TNF-? and placental transporters(CD36,FATP4 and FABPpm)in placental tissue were detected by Western Blot.The levels of long-chain polyunsaturated fatty acids in erythrocyte membranes of maternal blood and fetal blood were measured by GC-MS.Results: Differences in body weight between the CON group and the HFD group were observed after two weeks of high fat diet feeding(t=2.248,P=0.01).After 10 weeks of high-fat diet,according to the weight gain of the mice,the mouse in the HFD group were more than 20%,10% to 20%,and 10% of the average body weight of the CON group(n=12),and the mouse were recorded as DIO group(n=12),DIW group(n=15)and DIR group(n=12),respectively.The body weight of the four groups of mice was statistically significant(F=58.090,P<0.01).The average body weight of the DIR group was not different from that of the CON group(P=0.448).The average body weight of the DIW group and the DIO group was significantly higher than that of the CON group and the DIR group,and the differences were statistically significant(P<0.01).Compared with the CON group and the DIR group,the carcass ratios of the DIW group and the DIO group were significantly decreased,and the difference was statistically significant(P<0.05).Compared with the CON group,there was no change in the protein expression level of FADS1 in the DIR group,DIW group and DIO group(P>0.05);Compared with the CON group,the expression levels of FADS2 protein in the DIW group and the DIO group were significantly down-regulated(P<0.01).Compared with the DIR group,the expression level of FADS2 protein in the DIO group was down-regulated(P<0.01).Compared with the CON group and the DIR group,the expression levels of CD36 and FATP4 protein in the DIW group and the DIO group were down-regulated,and the difference was statistically significant(P<0.01).Compared with the CON group,only the expression levels of FABPpm protein in the DIW group and the DIO group were significantly downregulated,and the difference was statistically significant(P<0.01).The protein expression levels of IL-1? and TNF-? in the DIW group and the DIO group were significantly upregulated,and the difference was statistically significant compared with the CON group and the DIR group.After detecting the fetal red blood cell LC-PUFAs,the DHA level in the DIO group was significantly lower than that in the DIR group(P<0.05).The DIW group was found by detecting the level of LC-PUFAs in the red blood cells of the mother.The contents of ALA,DHA and EPA in the erythrocyte membrane of mouse were significantly higher than those in the CON group(P<0.05).The EPA content in the erythrocyte membrane of the DIO group was significantly lower than that in the DIW group(P< 0.05).Conclusions: Pre-pregnancy obesity caused a down-regulation of the desaturase FADS2 protein expression level.The results of this experiment showed that pre-pregnancy obesity may affect the LC-PUFAs nutrition level of offspring by down-regulating the expression levels of placental fatty acid transporters(CD36,FATP4 and FABPpm)and up-regulating the protein expression levels of placental inflammatory factors(IL-1? and TNF-?).Therefore,we hypothesize that pre-pregnancy obesity affects the nutrition of LC-PUFAs in offspring is that obesity promotes the up-regulation of placental inflammatory factors IL-1? and TNF-?,triggering placental tissue structure and dysfunction,which in turn causes placental fatty acids,and then down-regulation of the expression level of the transporter(CD36,FATP4 and FABPpm).