Maternal saturated fat diet induces decreases in detoxifying enzymes and oxidative tissue damage in the livers of fetuses and offspring

MAZZUCCO M. B; WHITE V; JAWERBAUM A; CAPOBIANCO E

Buenos Aires

Congreso; International Association of the Diabetes and Pregnancy Study Group (IADPSG); 2016

Maternal overweight programs metabolic alterations in the liver of the offspring. In a rat model of saturated fat overload in the maternal diet, we have previously found increased oxidative stress parameters and alterations in the gene expression of some detoxifying liver enzymes in the fetuses and offspring. The transcription factors Nrf2 and PPARalpha are implicated in the antioxidant/detoxifying cell defense. This involves induction of gene expression of a) detoxifying enzymes such as multidrug resistance-related proteins (MRPs) and b) antioxidant enzymes. Plasma activity of the liver enzymes glutamate oxalacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) are markers of liver damage.Objective: To investigate the effects of a saturated fat overload in the maternal diet on the livers from fetuses and 21- and 140-day-old offspring regarding a) Nrf2, PPARalpha and MRP3 gene expression, b) plasma GOT and GPT activity and c) nitrative-related tissue damage. Methods: Female Wistar rats were fed with either a standard (5% fat) or 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 pregnant rats were euthanized at 21 days of gestation, the fetal liver was explanted and fetal plasma obtained. Another group of control and SFD rats were allowed to deliver. The offspring were euthanized at 21 and 140 days of age, their plasma obtained and their livers explanted. All livers were preserved for the analysis of PPARalpha, Nrf2 and MRP3 gene expression (PCR), GOT and GPT activity (commercial kit) and 3-nitrotyrosine levels (immunohistochemistry). Results: Nrf2 expression in the livers from 21- and 140-day-old offspring (p