Butyrate increases maternal liver lipid accretion and ameliorates fetal markers of fatty liver programming.

FLORENCIA HEINECKE, JEREMÍAS PABLO FLORES QUIROGA, MARÍA AGUSTINA MENEGHINI, ALICIA JAWERBAUM, VERONICA WHITE.

Congreso; VIII Congreso de la Asociación Latinoamericana de Interacción Materno Fetal y Placenta (SLIMP); 2022

SLIMP

Objectives: We observed fetal markers of fatty liver disease in a rat model of maternal overweight. Those markers persisted in the adult offspring, pointing to the programming of this pathology. Maternal oral administration of Butyrate, a product of intestinal microbiota, prevented fetuses overgrowth and liver lipid overaccumulation; while in mothers increased liver Srebp-1c mRNA and consequently, liver lipid overaccumulation and decreased triglyceridemia.Our aim was to evaluate whether butyrate modulates the enzymes of hepatic lipid metabolism also involved in the programming of fatty liver.Methods: Female Wistar rats were fed standard (CT rats) or saturated fat rich-diet (FD rats) for 8 weeks and mated with control males. Butyrate (3%) or vehicle was orally delivered daily during gestation (FDB rats). At gestational day 21, rats were euthanized, maternal and fetal liversexplanted and weighed. mRNA levels of enzymes involved in lipid metabolism were assessed by RT-qPCR and alanine aminotransferase (ALT), marker of liver damage circulating activity, by EIA.Results: Maternal hepatic mRNA levels of Aco and Cpt-1 were decreased (30%p>0.05 vs CT) in FD and FDB rats. Fetal hepatic mRNA levels of Lpl, Srebp-1c and Cyp4a1 were increased (70%p>0.05 vs CT) in FD, while Butyrate prevented the increase in Srebp-1c and Cyp4a1 only 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 Butyrate (20%p>0.05 vs FD).Conclusion: Butyrate-induced downregulation of lipid oxidation enzymes may be involved in maternal liver lipid overaccumulation, while in fetuses, the prevention of overgrowth, liver lipid overaccumulation, and damage may involve sex-dependent pathways. Butyrate-induced prevention of fetal ALT levels and lipid accumulation may indicate prevention of fetal liver damage and consequently an improvement in metabolic programming.