The impact of maternal high fat diet on offspring brain, behaviour and cognitive functions

Abstract

The global rise in obesity and overweight, particularly among women of childbearing age, is escalating rapidly. High-fat diet (HFD)-induced maternal obesity is considered a contributing factor to neurodevelopmental disorders in their offspring, including depression, anxiety, ASD, ADHD. Rodent models have demonstrated that a maternal HFD during critical developmental periods has a lasting impact on the neurodevelopment of offspring, affecting both brain health and behaviour. To discriminate between maternal HFD and obesity, we hypothesise that maternal HFD during gestation/lactation or only preimplantation period, in the absence of obesity, influence offspring’s locomotor, explorative, anxiety-like behaviour, and social behaviours as well as memory functions. After conception, female-MF1 mice were allocated to one of three groups: Embryonic-HFD (EHFD), consuming the HF diet during the first 3.5 days of pregnancy, followed by a chow diet; HFD and control (NFD) groups, consuming HFD and chow diet throughout pregnancy/lactation, respectively. A series of behavioural tests were conducted on offspring from 9 HFD, 8 EHFD, and 9 NFD mothers, including the open field test (OFT) at weeks 4 and 10, to assess locomotor, exploratory, and anxiety-like behaviours; the novel object recognition (NOR) test at weeks 4 and 10 for short-term hippocampal memory; the elevated plus maze (EPM) at weeks 5 and 11, for anxiety-like behaviour; the T-maze at week 8 for spatial working memory; and the social interaction test (SIT) at week 12 for social behaviours. Following cryo-sectioning of adult offspring brains, hippocampal sections of male offspring were immuno-stained for Ki67 and doublecortin (DXC). mRNA expression levels of genes related to mitochondrial biogenesis (Tfam, Nrf-1, and Pgc1-alpha); oxidative stress and mitochondrial functioning (Nrf2, Sox2, and Cycs); cholesterol metabolism (ApoE, Hmgcs1, Lpl, and Fdps) and epigenetic mechanisms (Hdac1 and Dnmt1) were evaluated in the cortex and hippocampus of adult offspring using qPCR. Maternal HFD intake during the preimplantation period, led to reduced locomotor and exploratory behaviour in juvenile male offspring. Juvenile female offspring exposed to maternal HFD throughout gestation and lactation, exhibited potential signs of anxiety-like behaviour, although these behaviours were not observed in adulthood. Memory functions and social behaviour were not affected by maternal HFD. Additionally, there were no differences in the proliferation of immature neurons in the dentate gyrus of adult male offspring. The expression of selected genes associated with mitochondrial metabolism, cholesterol metabolism and epigenetic mechanisms showed no differences in both the hippocampus and cortex, except for one gene: the transcript levels of the master regulator of mitochondrial biogenesis, Pgc1-alpha, were increased in the cortex of adult female offspring, exposed to HFD during preimplantation or the whole pregnancy and lactation. These findings highlight that the future health of offspring can be influenced by exposure to an HFD in healthy, non-obese mothers. Importantly, these effects seem to be reversible in adulthood through normal diet consumption. This is the first time it has been demonstrated that maternal HFD, particularly during only preimplantation affects the offspring behaviour.

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ORCID for Sandrine Willaime-Morawek: orcid.org/0000-0002-1121-6419

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