Parental betaine supplementation promotes hepatic conversion of cholesterol to bile acids in offspring goslings with epigenetic modulation of CYP7A1 gene

Abstract

Objective: Maternal betaine supplementation has been shown to affect offspring metabolism through epigenetic mechanisms in mammals. This study aimed to investigate whether parental betaine supplementation can exert intergenerational effects on hepatic cholesterol metabolism in offspring goslings, and the possible epigenetic modification associated with such effects. Methods: In this study, 450 female and 90 male Jiangnan White goose breeders, aged 39 weeks, were randomly assigned to three groups receiving basal (control, CON), or betainesupplemented diets at low (LBT, 2.5 g/kg) or high (HBT, 5 g/kg) levels for 7 weeks. The breeder eggs laid in the last week were collected for incubation. Offspring goslings were slaughtered at 35 and 63 days of age to collect blood, bile, and liver samples for biochemical analysis and gene and protein expression studies. Results: The body weight of goslings in the LBT and HBT groups was significantly higher than that in the CON group (p<0.05). Serum and liver total cholesterol contents were significantly decreased in the HBT group (p<0.05), while the total bile acids contents in the liver and bile were significantly increased (p<0.05). These changes were associated with the upregulation of cholesterol-7 alpha-hydroxylase (CYP7A1) and bile salt export protein at both mRNA and protein levels (p<0.05). Additionally, parental betaine supplementation significantly decreased the DNA methylation level on the promoter region of the CYP7A1 gene (p<0.05). Conclusion: These results indicate that parental betaine supplementation decreases hepatic cholesterol content in offspring goslings through epigenetic modulation of the CYP7A1 gene.