Adult behaviour and cerebral cell densities after maternal or post-weaning consumption of an obesogenic diet in mice Emily Jane Mort Maternal obesity during pregnancy impairs cardiometabolic health of the adult offspring in experimental animals, and is associated with behavioural and cognitive impairments in human populations including increased rates of autism, attention deficit disorder and schizophrenia. Obesity in postnatal life has also been linked with increased risk taking behaviour and depression in teenagers and adults. Identifying whether these neurological changes are due to the pre- or postnatal environment is difficult in humans but is possible in experimental animals like mice. This study examined the independent effects of inducing maternal and post-weaning obesity by feeding a high fat, high sugar diet (HFHS) on the adult behaviour and brain cell densities of mice.

Under the Animal (Scientific Procedures) Act, C57BL6/J female mice were fed either a control (Con, 11%kcal fat, 7%kcal simple sugars) or HFHS diet (37.9%kcal fat, 33.0%kcal simple sugars) from 6 weeks before pregnancy and throughout pregnancy and lactation. Offspring from HFHS fed mothers were weaned onto the control diet (HFHSC) while a subset of control offspring were weaned onto the HFHS diet to create a post-weaning obesity group (CHFHS).The HFHS diet significantly increased body fat percentage of the females before pregnancy (Con 20.7±0.6% vs. HFHS 32.3±2.0%). A subset of pregnant dams were killed at day 18.5 of pregnancy for fetal tissue collection while the rest delivered naturally, with litters reduced to 6 at postpartum day 2. Behaviour of male and female 12 weeks old offspring was tested using an elevated plus maze (EPM for anxiety), open field (for anxiety and locomotion), social interaction (for social preference) and novel object recognition (for object recognition memory) tasks. At 14 weeks of age, the offspring were killed and their brain collected for regional analysis of neuron and glia densities. Behavioural and cell density data were analysis by two-way ANOVA with post hoc Sidak’s multiple comparison test or by unpaired t-test, where appropriate. Data expressed as mean ±SEM.

At day 18.5 of pregnancy HFHS pups were growth restricted relative to controls, with this restriction maintained until postnatal day 7, after which HFHS offspring displayed catch up growth. Maternal consumption of the HFHS diet led to increased adiposity and reduced adrenal gland mass in adult male HFHSC offspring. CHFHS mice significantly increased body mass and adiposity while adult male CHFHS mice reduced adrenal gland mass. No difference for brain mass was seen in either fetal or adult HFHSC or CHFHS mice. Maternal and post-weaning obesity reduced anxiety within the EPM task and impaired object recognition memory. Post-weaning obesity also resulted in increased social interaction for male and female mice as well as reducing locomotion in males. Reduced Iba1+ microglia density was found within the basolateral amygdala for both HFHSC and CHFHS offspring, as well as reduced NeuN+ neuron density for HFHSC offspring and CHFHS females accompanied by increased GFAP+ astrocyte density within the perirhinal cortex for HFHSC and CHFHS females. Overall, consumption of the HFHS diet post-weaning led to a larger range of adult behavioural changes and more robust alterations to cerebral cell densities than maternal consumption alone.