Gender-divergent Expression of Lipid and Bile Acid Metabolism Related Genes in Adult Mice Offspring of Dams Fed a High-fat Diet

Maternal high-fat diet (HFD) consumption during pregnancy and lactation affects metabolic outcomes and lipid metabolism of offspring in later life in a gender-specific manner. However, it is not known whether maternal HFD alters bile acid metabolism in adult mice offspring. The purpose of this study was to elucidate the relationship between maternal HFDinduced metabolic diseases and bile acid metabolism in male and female adult mice offspring. Female mice were fed either standard chow (C) or HFD (H) for 10 weeks pre-pregnancy until lactation. After weaning, offspring were fed a chow diet until 11 weeks of age, then challenged with either C or H diet for 4 weeks, and divided into eight groups in accordance with mother's and offspring's diets: male(M) CC, MHC, MCH, MHH, female(F) CC, FHC, FCH, and FHH. MHH showed greater weight gain compared to FHH. Liver weight was higher in MHH than in FHH. Serum total cholesterol levels were higher in MHH than in MHC, and tended to be higher in MHH than in FHH. Serum glucose levels were higher in MHH than in MHC. Hepatic triglyceride levels were higher in MHH than in MHC. Hepatic mRNA expression of bile acid uptake transporters Oatp1a1 and Oatp1b2 was increased in MHH, compared to MCH. Hepatic mRNA expression of HMGCoAR, Cyp7a1, Sult2a1, and Oatp1a4 was increased in FHH, compared to FCH. In conclusion, maternal HFD consumption may promote bile acid synthesis, sulfation and excretion in female offspring fed a HFD, which may confer resistance to HFDinduced metabolic phenotypes.