Maternal treatment with sodium butyrate prevents fetal macrosomia and reduces the expression of lipid transporters in placentas from overweight rats.

Abstract

Objective: Maternal obesity/overweight induces anomalies in fetuses and placentas that precede the programming of metabolic derangements in the offspring. Butyrate, a short chain fatty acid product of fiber metabolism from the intestinal microbiota, improves lipid and glucose homeostasis. We aimed to study whether oral administration of butyrate prevents alterations in pregnancy outcomes and ameliorates lipid metabolic anomalies in placentas from overweight rats. Methods: Female rats were fed with standard (CT group) or saturated fat-rich-diet (26 %fat) since they were 6-week old (FD group). After 8 weeks CT and FD rats (15% overweight) were mated with control males. FD pregnant rats were orally treated with 3% sodium butyrate or vehicle daily during gestation (FD+B group). At day 21 of pregnancy the rats were euthanized, fetuses and placentas obtained, and their weight registered. Placental lipid levels were assessed by TLC and mRNA levels of genes involved in feto-placenta lipid transport, by RT-qPCR. Results: FD fetuses were heavier than controls (5% p<0.05), alteration prevented by butyrate (6% p<0.05 compared to FD). Litter size was increased in the FD group (20%p<0.01) compared to controls and in the FD+B group (13%p<0.05) compared to the FD group. FD placentas showed lipid overaccumulation (Cholesterol 100%, Free-fatty-acids 160%, Triglycerides 100% and Cholesteryl Esters 60%, p<0.05), in line with an upregulation of placental mRNA levels of lipoprotein-lipase (70% p<0.05), fatty-acid-binding-protein5 (58% p<0.01) and perilipin2 (57% p<0.05) compared to controls. Despite lipid overaccumulation persisted in the FD+B group, mRNA levels of the lipid transporters evaluated were reduced in the FD+B group (70%, 40%, 33% p<0.05 respectively), compared to the FD). Conclusions: Maternal overweight induces fetal macrosomia and placental lipid overaccumulation which might be sustained by an increased placental uptake and transport of lipids to the fetus. Butyrate prevents fetal macrosomia and normalizes placental lipid transporters expression, which might be reducing feto-placenta lipid transport and preventing fetal overgrowth.