This work aimed to investigate whether

This work aimed to investigate whether the increase in liver lipid depots, observed in the fetuses from rats fed a saturated-fat-rich diet, persists later in life in the offspring (a) at 21days of age immediately after weaning and (b) at 140days of age, after healthy nourishing. Furthermore, we wanted to investigate if leptin resistance could be involved in the programming of lipid liver alterations and to establish a role for fetal hyperleptinemia in the programming of alterations in liver lipid homeostasis.
Materials and methods
Results
Discussion The data presented here show many alterations in lipid metabolism in the livers of the offspring born to rats fed a 26% saturated-fat-rich diet (SFD rats). We evidenced similar lipid metabolism alterations in fetuses and in offspring 21days of age and 140days of age. A relevant finding was that livers of fetuses from SFD mothers displayed no changes when exposed to leptin, suggesting in utero leptin resistance. We also provide data suggesting that fetal hyperleptinemia could be involved in the development of liver lipid Tanespimycin australia impairments. We have previously shown that SFD rats display an increase in maternal weight gain during pregnancy and that their fetuses were macrosomic [24]. In this work, the offspring of 21days of age from the SFD group were heavier and exhibited heavier livers than controls. Later in life, offspring of 140days of age born to SFD rats showed no changes in body weight or liver weight when compared to controls. The young offspring showed increased triglyceridemia and liver lipid overaccumulation, while the elder offspring showed unchanged lipid plasma profile and did show the liver lipid overaccumulation. Other researchers have shown that adult offspring of rats fed high-fat diets (60% calories from fat) that continue or not eating the high-fat diet after weaning display fatty livers together with overweight and hypertriglyceridemia [28], [44], [45]. The 140-day-old offspring of both groups ate regular rat chow from weaning to sacrifice, and this might be the reason why the adult offspring from SFD rats exhibited no overweight or hypertriglyceridemia as the young offspring. Nevertheless, without the high lipid caloric input, they still maintained the liver lipid metabolism anomalies. Moreover, in our study, maternal saturated-fat-rich diet has 45% calories from fat and adult offspring evidenced liver alterations without overweight or hyperlipidemia. These results highlight the importance of the dietary composition, not only for the final caloric input but also for the source of energy used for maternal nourishing. Our investigation shows that liver damage can be induced in the offspring by the maternal diet despite having healthy nutrition from weaning. Aiming to find a reason for the increase in liver lipid levels in the offspring from SFD rats, we studied the expression of PPARα, CPT1 and ACO, key genes involved in the lipid catabolism of the liver. We found that livers from fetuses and offspring from SFD rats showed several alterations depending on the age and on the gender. CPT1 expression was decreased in fetuses, young offspring and male adult offspring, while ACO expression was decreased in male fetuses and in young and adult offspring. The decrease in these enzymes could be implicated in the development of liver lipid overaccumulation. The offspring that received high saturated fat input during perinatal life could have adapted to down-regulate the lipid catabolism machinery, reducing fat utilization as energy source. The development of this adaptation might be the cause of liver lipid overaccumulation that induces lipotoxicity and is harmful for liver function [46], [47]. PPARα expression showed no changes in all the developmental stages studied. Several works have shown decreased expression of ACO and CPT1 (targets of PPARα), together with clear markers of fatty liver disease [48], [49], [50], [51]. As PPARα activity regulates the expression of both CPT1 and ACO [36], [52], [53], the fact that ACO and CPT1 are down-regulated independently of PPARα expression might indicate a decrease in PPARα activity in the SFD group.