Maternal saturated fat-enriched diet determines leptin resistance in the fetal liver and programs lipid homeostasis impairment in the offspring

MARÍA BELÉN MAZZUCCO, DAIANA FORNES, ALICIA JAWERBAUM AND VERÓNICA WHITE

Mar del Plata

Congreso; VI SLIMP Latin American Symposium on Maternal Fetal Interaction and Placenta.; 2015

SLIMP

Maternal obesity leads to impaired metabolic programming. In a rat model of saturated fat overload in the maternal diet, we have previously found increased fetal liver lipid content. Lipid catabolism in the liver assures proper lipid homeostasis. Leptin regulates lipid catabolism in several tissues. Objective: To investigate whether an overload of saturated fat on the maternal diet impairs leptin effects on hepatic lipid catabolism in rat fetuses at term gestation and whether these anomalies are sustained in the offspring of these rats. Methods: Female Wistar rats were fed with a standard (5% fat) or with a saturated fat diet (28% fat) from 6 weeks of age (SFD rats). After 8 weeks of diet, they were mated with control males. Control and SFD rats were euthanized at 21 days of gestation and fetal livers obtained for further culture of explants (3h) with or without leptin (100 ng/ml). Another group of control and SFD rats were allowed to deliver, and their offspring euthanized at 21 or 130 days of age. Livers were analyzed for lipid accumulation (TLC) and acylCoA oxidase (ACO) expression (PCR). Results: Leptin induced a decrease in triglycerides (49%), free fatty acids (75%) and cholesteryl esters (42%) concentrations in fetal livers from control rats (p lower than 0.05), but no changes but no changes in fetal livers from SFD rats, which showed. Leptin induced an increased ACO expression (50%, p lower than 0.05) in control fetal livers. Fetal livers from SFD rats showed a decrease in ACO expression (25% p lower than 0.05) and no changes with leptin additions. A decrease in ACO expression were also observed in the livers of 21- and 130- day-old offspring from SFD rats (20%, p lower than 0.05). Conclusions: Saturated fat in maternal diet induces hepatic lipid metabolism impairment in fetuses and offspring. Liver leptin resistance on lipid catabolism begins in utero and maybe responsible for the alterations on the offspring lipid metabolism.