Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas

Abstract

Metabolic alterations in obese and overweight mothers impact the placenta and the fetus, leading to anomalies in fetal growth and lipid accretion. The primary aim of the study was to examine the effect of a saturated fat-rich diet (FD) on growth, lipid accretion, and lipases, leptin and leptin receptor (ObR) expression in the placenta and fetal liver. We also aimed to find a role for fetal leptin in the modulation of placental and fetal liver lipase and ObR expression. Six-week-old rats were fed with a standard rat chow (control) or a 25% FD for 7 weeks until mating and during pregnancy. Also, in a group of control rats, fetuses were injected with leptin on days 19, 20, and 21 of pregnancy. On day 21, we assessed lipidemia, insulinemia, and leptinemia in mothers and fetuses. In the placenta and fetal liver, lipid concentration was assessed by thin layer chromatography (TLC) and the gene expression of lipoprotein lipase (LPL), endothelial lipase, insulin receptor (Insr), leptin, and ObR by RT-PCR. The FD induced hypertriglyceridemia and hyperleptinemia (P!0.01) in mothers and fetuses, an increase in maternal (P!0.05) and fetal weight (P!0.01), overaccumulation of lipids in fetal liver (P!0.01), and enhanced leptin expression in the placenta and fetal liver (P!0.05). Placental expression of IR and LPL was increased (P!0.05), and ObR decreased (P!0.05) in the FD group. Fetal administration of leptin induced the placental and fetal liver downregulation of ObR (P!0.05) and upregulation of LPL expression (P!0.05). The FD led to increased fetal lipid levels, which may result from high maternal lipid availability and fetal leptin effects. Key Words" Saturated fat-rich diet

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

“…Aiming to establish the role of fetal circulating leptin in the modulation of the fetal liver expression of genes involved in lipid catabolism, we administered leptin to fetuses at term gestation, as described previously [24]. Briefly, on day 19 of gestation, a group of control mothers were shortly anesthetized with slight vapors of ether.…”

“…Fetal livers were carefully removed, stored in RNAlater and kept at −20°C for future PCR analysis. The concentration was chosen based on previous in vivo studies that showed the effects of 20 ng of leptin on fetal liver gene expression [24]. Plasma leptin levels were assessed in the saline-injected and leptin-injected fetuses, for validation of the method.…”

“…Since then, many investigations have demonstrated that maternal overweight also induces metabolic alterations from fetal life to adulthood in the offspring [9,14,16,17]. We and others have described metabolic abnormal outcomes in fetuses from rats fed with different approaches of diets rich in saturated fat, with increases in caloric input [18][19][20]. Many metabolic alterations have been described in fetuses and offspring from mothers with metabolic impairments [21][22][23][24].…”

“…We and others have described metabolic abnormal outcomes in fetuses from rats fed with different approaches of diets rich in saturated fat, with increases in caloric input [18][19][20]. Many metabolic alterations have been described in fetuses and offspring from mothers with metabolic impairments [21][22][23][24]. Lipid metabolic alterations harm the liver, which is an important organ for lipid homeostasis and lipid trafficking through the organism.…”

“…The transcription factors PPARα and STAT-3 mediate the expression of leptin-induced lipid catabolic enzymes [32,37], such as the acetyl-CoA oxidase ACO and the carnitine palmitoyl transferase CPT1 [38,39]. We have shown that fetuses from rats fed a saturated-fat-rich diet through pregnancy and lactation display hyperleptinemia and liver lipid overaccumulation [24].…”