Critical periods of increased fetal vulnerability to a maternal high fat diet

Abstract

BackgroundFetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression.MethodsFemale wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, 9.5% fat) for 2 wk before mating until e9.5 of pregnancy (periconception-midpregnancy). At e9.5 dams were switched to the opposite diet (C-HF or HF-C).ResultsExposure to HF diet throughout pregnancy reduced maternal weight gain compared to C diet (p < 0.02 HF vs. C). HF-C dams had significantly decreased adiponectin levels and litter size when compared to C-HF (p < 0.02 HF-C vs C-HF). Independent of the timing of exposure to HF, fetal weight and length were significantly decreased when compared to C diet (HF, C-HF and HF-C vs. C p < 0.02). HF diet during the second half of pregnancy increased expression of genes in the fetal liver associated with fetal growth (C-HF vs C p < 0.001), glucose production (C-HF vs C p < 0.04), oxidative stress and inflammation (C-HF vs C p < 0.01) compared to C diet.ConclusionsThis model defines that there are critical periods during gestation in which the fetus is actively shaped by the environment. Early exposure to a HF diet determines litter size while exposure to HF during the second half of pregnancy leads to dysregulation of expression of key genes responsible for fetal growth, hepatic glucose production and oxidative stress. These findings underscore the importance of future studies designed to clarify how these critical periods may influence future risk of developing MetS later in life.

Role of placental insufficiency and intrauterine growth restriction on the activation of fetal hepatic glucose production

“…An early activation of gluconeogenic gene expression has also been observed in animal models of maternal over nutrition or high fat diet exposure in mice, rats, sheep, and non-human primates (McCurdy et al, 2009, Plata Mdel et al, 2014, Rattanatray et al, 2014, Strakovsky et al, 2011, Zhou et al, 2015). The mechanisms for the activation of gluconeogenic genes during intrauterine exposures to increased or decreased nutrients remain unclear.…”

The effect of maternal Inflammation on foetal programming of metabolic disease

“…Interestingly, in mice, the foetus is more susceptible to maternal high‐fat feeding in the latter part of pregnancy, than in the earlier part (Plata et al . ).…”

“…These data show that the placenta prevents and enhances the transport of immune components differently during the first, second and third trimester, perhaps due to a fluctuating need for different nutritional and regulatory components during foetal development. Interestingly, in mice, the foetus is more susceptible to maternal high-fat feeding in the latter part of pregnancy, than in the earlier part (Plata et al 2014).…”

Maternal fructose drives placental uric acid production leading to adverse fetal outcomes

“…However, in the absence of metabolic diseases, consumption of sucrose and sugar-sweetened beverages can also increase the risk for developing preeclampsia 12 13 . It is well established that nutritional and other environmental exposures during fetal development can permanently affect the composition, homeostatic systems, and functions of multiple organs and systems 14 15 . Thus, pregnancy complications predispose the offspring to poor metabolic health in adulthood 16 .…”