MATERNAL FAT OVERFEEDING PROGRAMS ALTERATIONS IN PPAR ALPHA PATHWAYS RELATED TO LIPID METABOLISM IN LIVERS FROM RAT FETUSES AND ADULT OFFSPRING

MAZZUCCO, MARÍA BELÉN; JAWERBAUM, ALICIA; MAZZUCCO, MARÍA BELÉN; JAWERBAUM, ALICIA; FORNES, DAIANA; WHITE, VERÓNICA; FORNES, DAIANA; WHITE, VERÓNICA; HEINECKE, MARÍA FLORENCIA; CAPOBIANCO, EVANGELINA; HEINECKE, MARÍA FLORENCIA; CAPOBIANCO, EVANGELINA

Varadero

Taller; "Animal Models and Preclinical Research 2019" (AniMod 2019); 2019

El Centro de Ingeniería Genética y Biotecnología de La Habana (CIGB), la Sociedad Cubana de Farmacología y el Centro Nacional para la Producción de Animales de Laboratorio (CENPALAB)

MATERNAL FAT OVERFEEDING PROGRAMS ALTERATIONS IN PPAR ALPHA PATHWAYS RELATED TO LIPID METABOLISM IN LIVERS FROM RAT FETUSES AND ADULT OFFSPRINGWe have developed a model of rat overweight by feeding rats with a saturated fat-rich diet (SFD rats). Livers from fetuses and adult offspring from these rats show lipid overaccumulation and decreased expression of the genes involved in lipid catabolism. Aim: to analyze if the clofibrate, a pharmacological activator of PPARalpha is able to induce lipid catabolism by increasing the transcription of PPAR target genes involved in lipid catabolism in livers from fetuses and adult offspring from the SFD rats.Female Albino-Wistar rats were fed with standard or a saturated fat-rich diet since they were 6 week-old. After 8 weeks, both groups were mated with control males. The fatty diet was achieved by combining 25 grs of melted butter with 75 g of standard chow. Both groups continued with their respective diets during pregnancy and lactation. Control and SFD rats were euthanized at gestational day 21 or allowed to deliver and their offspring euthanized at 140 days of age. Offspring and fetal livers were explanted and cultured with or without clofibrate. By TLC we analyzed the lipid content in the fetuses and adult offspring livers and we observed that clofibrate decreased liver lipid levels in the control group. Moreover, we analyzed the mRNA levels of genes involved in lipid metabolism by qRT-PCR and we found an upregulation in their levels in livers cultured with clofibrate from fetuses and adult offspring from the control group. Differently, fetuses and adult offspring from SFD rats showed no response to PPAR activation in their livers, neither in lipid levels, nor in mRNA levels.Maternal fat overfeeding induces a resistance to the lipid metabolic effects of PPAR, alteration probably involved in the liver lipid overaccumulation in the offspring from SFD rats. The use of oral fibrates might not be efficient for the treatment of the fatty liver programmed by maternal obesity.