Gestational treatment of butyrate modulates maternal and fetal lipid metabolism in a rat model of maternal overweight

EVANGELINA CAPOBIANCO; FLORENCIA HEINECKE; ALICIA JAWERBAUM; CINTIA GATTI; VERÓNICA WHITE

Congreso; Reunión anual de Sociedades Biocientíficas (SAIC 2021); 2021

In a rat model of maternal overweight we described in mothers, hypertriglyceridemia and in fetuses, overgrowth and liver lipid overaccumulation. Fetal alterations persisted in the offspring that develop fatty liver disease. Butyrate (B), a product of fiber metabolism from intestinal microbiota, improves lipid metabolism and prevents inflammation. Maternal oral administration of B prevented maternal hypertriglyceridemia, fetal overgrowth and liver lipid overaccumulation.Our aim was to clarify the effects of B on lipid metabolism that helped to prevent maternal and fetal alterations.MethodsFemale Wistar rats were fed standard (CT rats) or saturated fat-rich-diet (FD rats) for 8 weeks and mated with control males. Vehicle or B (3%) was orally delivered daily during gestation (FDB rats). At gestational day 21, all rats were euthanized. Fetuses, maternal and fetal liver were explanted and weighed. Maternal liver levels of triglycerides (TG) were assessed by TLC, mRNA levels of enzymes involved in lipid metabolism by RT-qPCR and alanine aminotransferase (ALT) circulating activity by EIA.ResultsMaternal livers showed TG overaccumulation in FD rats (300% p>0.01 vs CT) which persisted in FDB rats. Maternal hepatic mRNA levels of Aco and Cpt-1 were decreased (30%p>0.05 vs CT) in FD and FDB rats, while Srebp-1c mRNA levels were increased in FDB rats (40% p>0.05 vs CT). Fetal hepatic mRNA levels of Lpl and Srebp-1c were increased (70% p>0.05 vs CT) in FD, while B prevented the increase in Srebp-1c in female fetuses (60% p>0.05 vs FD). FD fetuses showed an increase in ALT activity (30% p>0.05 vs CT), which was prevented by B (20% p>0.05 vs FD).ConclusionsButyrate increased the already FD-induced maternal liver lipid overaccumulation. A decrease in lipid oxidation enzymes and an increase in Srebp-1c expression may be involved in maternal effects, while in fetuses, prevention of overgrowth, liver lipid overaccumulation and damage may involve sex dependent pathways.