title: Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.
abstract: We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.
authors.affiliation: Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, School of Medicine, University of Buenos Aires, 1053 Buenos Aires, Argentina.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Mazzucco
authors.affiliation: Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, School of Medicine, University of Buenos Aires, 1053 Buenos Aires, Argentina.
authors.forename: Daiana
authors.initials: D
authors.lastname: Fornes
authors.affiliation: Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, School of Medicine, University of Buenos Aires, 1053 Buenos Aires, Argentina.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.affiliation: Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, School of Medicine, University of Buenos Aires, 1053 Buenos Aires, Argentina.
authors.forename: Romina
authors.initials: R
authors.lastname: Higa
authors.affiliation: Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, School of Medicine, University of Buenos Aires, 1053 Buenos Aires, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
authors.affiliation: Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, School of Medicine, University of Buenos Aires, 1053 Buenos Aires, Argentina. Electronic address: vernica73@gmail.com.
authors.forename: Verónica
authors.initials: V
authors.lastname: White
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D006706:Homeostasis; D020738:Leptin / Q000502:physiology*; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004041:Dietary Fats; D020738:Leptin
keywords: Fetus; Leptin; Liver lipid catabolism; Offspring; Saturated-fat-rich diet