| Objective Inthis study, we used a cross-fostering paradigm to determine whether maternal high fat diet(HFD) feeding during pregnancy and/or lactation is more critical in offspring fetal growth and metabolic programming and to explore the possible pathways underlying this phenomenon in the early life of rat offspring. The results may provide scientific experimental basis for the prevention of intrauterine dysplasia and metabolic disorder caused by maternal HFD feeding. Methods Here using ICR mice, pregnant rats were maintained on normal chow(CD) or HFD during gestation and/or suckling. All litters were cross-fostered to CD or HFD dams on postnatal day(PND) 1, resulting in four groups:(1) CCD(2) CHD(3) HCD(4) HHD. We examined the effects on the dams and on the offspring at birth and weaning. At the end of pregnancy, the dams were performed a caesarean operation under 10% chloral hydrate anesthesia(0.3ml/100 g body weight i.p.) after 10-h of fasting for dams for sample collection, including placenta and neonates liver.Milk quantity was measured per 3 days from PND1 to PND18, the body weight of offspring was measured from PND1 to PND21 per 3days. Energy intake, body weight, birth weight, Blood parameters were measured, serum insulin level, and glucagon level, triglyceride(TG) and total cholesterol(TC)) were measured at weaning. RT-PCR was performed to detect mRNA expression levels of placental and liver tissues. Placental and liver tissues amino acid transporter(CD36, Fatp1 and Fatp4) and Srebp-1 protein expression levels were detected by Western Blot. Results At the end of pregnancy(GD18), in offspring, HFD group had a significantly higher serum glucose(P=0.008), placental weight(P =0.004) and serum TC level(P=0.014) compared with CON group. While decreased in serum insulin level(P=0.058). Placental tissues fatp4 were obviously up-regulated in HFD rats(P=0.034). Compared with CON group, placental FATP4 protein expressionwere higher in HFD group, but there is no significance.Dams cross-fostered to HFD produced more milk than postnatal Con diet group dams by PND6 and persisted until weaning.There was no difference in milk composition in PND14. In PND21, There was a significantly higher in serum TG level in HCD group than HCD group in male offspring and CCD group was higher than postnatal HFD feeding pubs in female pubs. Pups cross-fostered to HFD gained more body weight than chow pups by PND6 and persisted until weaning both in male and female offspring. In PND21, CCD group had a lowest bodyweight than any other groups and HHD group was the highest and there were no significantly differences among CHD, HCD, HHD groups in male offspring. In female offspring, HHD group had a highest bodyweight than the three groups and CCD group was the lowest(P<0.05), CHD and HCD had a similar bodyweight.In offspring, Pups cross-fostered to HFD were higher in liver weight,gonadal fat,perirenal fat than Pups cross-fostered to HFD. HHD group had a higher kidney weight than any other groups and CCH group was the lowest.Pups cross-fostered to HFD had a significantly higher serum TC level than those that postnatal Con diet group(P<0.05) in male offspring, there is no significantly difference in serum TG. However, CCD group had a higher serum insulin level than CHD and HCD groups(P<0.05), pups cross-fostered to HFD diet had a significantly higher FBG than CCD group, CHD group had a significantly higher glucagon level than HCD group both in male and female offspring,Postnatal Con group(CCD and HCD) had a higher serum insulin level(P<0.05), however, there is no significantly different in all groups in female offspring even if CCD is increased. In PND21, Histopathology showed that hepatic lipid accumulation was observed in postnatal HFD pups but not in postnatal Con pups both in male and female pubs.There was a significant effect of maternal HF diet on FATP4, Srebp-1 expression with increased expression in liver tissues(P<0.05), no significantly difference was observed among CCD, HCD, HHD groups in male offspring, indicating that HFD only in lactation has a greater stimulatory effect.Western-Blot indicating that fatp4 was downregulated in HHD group both in male and female offspring. There were no differ in Srebp-1 and CD36 protein expression both in male and female offspring. Conclusion This study suggested that maternal HF diet during lactation had impact on milk production and pup metabolic phenotype regardless of maternal diet during pregnancy. We argued that maternal HF diet during lactation may influence the metabolic phenotype of offspring because it increased milk production, leading to an assumption that pups could intake increased amount of milk. |
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