(P23-21-26) Maternal One-Carbon Metabolism Nutrients Supplementation to a High-Fat, High-Sucrose Diet Attenuates Hepatic Lipid Anabolism in Offspring

Objectives: Perinatal one-carbon metabolism nutrients (OCMN) play a pivot role in programming offspring lipid metabolism. We aimed to examine whether OCMN supplementation to a maternal obesogenic diet during gestation and lactation affect hepatic lipid anabolism in offspring in a sex-specific manner.

Methods: After mating, pregnant Sprague-Dawley rats (n = 10/group) were randomly assigned to AIN93G control (CON) diet, 45% fat diet with sucrose (HFS), or HFS diet supplemented with folic acid, B₁₂, betaine, choline, zinc, and methionine (HFS-OCMN) during gestation and lactation. At weaning, pups (n = 10/sex/group) were randomly assigned to a CON or HFS diet until 15 weeks of age. Biomedical index and hepatic fat anabolic gene (SREBP1-1c and FASN) expression was measured. Data was analyzed by ANOVA followed by post hoc tests as appropriate.

Results: In male pups, OCMN supplementation suppressed elevation of hepatic TG (P = 0.010) and serum LDL (P = 0.033) and reduction of serum HDL (P = 0.046) induced by maternal HFS. In female pups, OCMN supplementation only restored low serum HDL (P = 0.037) induced by maternal HFS. Pups’ diet did not alter the above variables. Hepatic SREBP-1c gene expression was lower in pups of dams fed with HFS-OCMN than that in pups of dams fed with in HFS and CON regardless of offspring diet in both sexes (males: 0.73 ± 0.06 vs. 1.04 ± 0.09, P = 0.030, and 1.08 ± 0.12, P = 0.046; females: 0.58 ± 0.11 vs. 1.07 ± 0.11, P = 0.008, and 1.42 ± 0.10, P < 0.001). FASN gene expression did not differ across groups in males. In female pups, OCMN supplementation to dam’s HFS reduced FASN gene expression, compared to dam’s HFS (P = 0.002).

Conclusions: Maternal OCMN supplementation to HFS diet reduced hepatic SREBP-1c expression in offspring of both sexes, lowered hepatic TG and LDL, and increased HDL in male pups, and reduced hepatic FASN gene expression in female pups, without significant effects on female pups’ circulating lipids.

Funding Sources: Texas State University REP grant