Maternal saturated fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring

MARÍA BELÉN MAZZUCCO; ROMINA HIGA; DAIANA FORNES; EVANGELINA CAPOBIANCO; ALICIA JAWERBAUM.

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2016 vol. 27 p. 61 - 69

0955-2863

Maternal obesity has been linked to the development of many metabolic alterations in the offspring. 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 with a diet rich in saturated fat (SFD rats) or regular diet (controls). Lipid levels were assessed in plasma and livers from fetuses and 21- and 140-day-old offspring from control and SFD rats. Gene expression of carnitin palmitoil tranferase-1 (CPT1), peroxisome proliferator-activated receptor alpha (PPARalpha) and acetyl CoA oxidase (ACO) was assessed in livers of fetuses and offspring from controls and SFD rats. Fetal livers from both dietary groups cultured in the presence of leptin were studied for lipid levels and gene expression. Leptin or vehicle was administered to control fetuses during the last days of gestation. At term gestation, fetal livers were obtained and gene expression assessed. Liver lipid levels were increased and CPT1 and ACO were downregulated in fetuses, 21- and 140-day-old 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 saturated fat overload in maternal diet induces fetal leptin resistance that might be priming liver lipid alterations that are sustained in the offspring.