High fat diet‐induced maternal obesity alters fetal hippocampal development

Abstract

The importance of maternal nutrition for fetal brain development is increasingly recognized. Previous studies have suggested that maternal obesity or maternal exposure to obesogenic diets may permanently alter brain structure and function in the offspring. To test whether maternal exposure to a high-fat diet, prior and during gestation, alters fetal hippocampal development, we fed 8-week old C57BL/6 females with a high-fat diet (60% calories from fat) for 10 weeks prior to matting and 17 days after. Fetal brains at embryonic day E17 were used to determine developmental changes in the hippocampus. We report that maternal exposure to the high-fat diet induced small for gestational age (SGA) status and fetal resorption. The proliferation of neural progenitors was increased in the neuroepithelium from hippocampus and cortex in fetuses from mothers fed the high-fat diet when compared to controls, but decreased within the dentate gyrus (DG). Apoptosis in the hippocampus was decreased (Ammon’s Horn and fimbria). The differentiation of calretinin-positive neurons within the DG was also decreased. These data indicate that, under the influence of a maternal high-fat diet administered prior and during gestation, fetal hippocampal development is altered at embryonic day 17, as indicated by region-specific changes in proliferation of neural precursors, decreased apoptosis, and by decreased neuronal differentiation within the dentate gyrus.

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

“…In total, more and heavier fetuses and placentas contribute to the increase in maternal weight gain, as seen by others (Jones et al 2009). Conversely, other experimental models fed with high-fat diets have shown a decrease in fetal weight, and a diminished placental efficiency, calculated by a fetal-to-placental weight ratio (Niculescu & Lupu 2009, Hayes et al 2012. In this study, we show an increase in fetal weight, together with an increase in placental weight, and this increase in placental mass might contribute to an enhancement of maternal-to-fetal nutrient transport, inducing an increase in fetal growth.…”

“…A report of the WHO and FAO in 2003 suggested a dietary intake between 15 and 30% of calories from fat in humans (www.who.int/mediacentre/news/ releases/2003/pr20/en). The saturated fat-rich diet used in this study has 47% of calories from fat, a value higher than the one recommended for both rat and human intakes, but lower than that of other high-fat diets used in rodents in which fat contribution to total calories is 60% (Niculescu & Lupu 2009) and 58% (Softic et al 2012).…”

The Role of Nutrition in Children's Neurocognitive Development, From Pregnancy Through Childhood

“…Furthermore, when rats were fed a high fat diet, it decreased neurogenesis in the hippocampus (Lindqvist et al, 2006). In addition, a maternal high-fat diet in mice altered the development of hippocampus in the foetus (Niculescu and Lupu, 2009), which may mediated by a decrease in the level of brain-derived neurotrophic factor (Molteni et al, 2002). A recent literature review concluded that overweight and obesity may result in poorer academic performance (measured as literacy, numeracy, and school grades; Burkhalter and Hillman, 2011), but only a few studies have researched a possible connection between obesity/overweight and cognitive performance.…”

Maternal high-fat diet during pregnancy or lactation changes the somatic and neurological development of the offspring

“…Within this context, fetuses and newborns are increasingly exposed to maternal HFD which may cause problems in growth and brain deve lopment 4 . However, few stu dies ha ve investigated the effects of maternal HFD on the brain development of the offspring 5,6, particularly isolating or separating the periods of pregnancy and lactation. On the other hand, most studies have evalua ted the effects of maternal obesity or HFD intake along gestation and lactation, hindering the identification of the "best window" for altering developmental or physiological programming 7,8. In addition, according to epidemiological and experimental studies, nutritional status and/or maternal nutrition du ring prenatal and early postnatal periods play an important role in epigenetic mechanisms involved in the developmental origins of non-communicable disease, such as obesity, metabolic syndrome, type 2 diabetes and cardiovascular disorders [9][10][11] , and phenotypic plasticity in response to environmental cues [9][10][11] .…”