UK rates of adult obesity have doubled in the last 25 years, leading to more overweight pregnant women (1). Maternal obesity during pregnancy impairs cardiometabolic health of the adult offspring in experimental animals, and is associated with behavioural and cognitive impairments in humans (2,3). Identifying whether these neurological changes are due to the pre- or post-natal environment is difficult in humans but is possible in experimental animals like mice. This study examined the effects of maternal obesity on the behaviour of their adult offspring fed standard chow post-weaning. Under the Animal (Scientific Procedures) Act, C57BL6/J female mice were fed either a control (Con, 11%kcal fat, 7%kcal simple sugars) or high fat-high sugar diet (HFHS, 35.9%kcal fat and 29.5%kcal simple sugars) from 6 weeks before pregnancy and throughout pregnancy and lactation. The HFHS diet significantly increased body fat percentage of the dams before pregnancy (Con 20.8±0.6% vs. HFHS 32.5±1.7%, p<0.0001). Pregnant dams delivered naturally and their litters were reduced to 6 at postpartum day 2 (PN2). All offspring were weaned onto the control diet. From 12 weeks of age male and female offspring were tested using an elevated plus maze (EPM for anxiety; Con n=13 ♀, n=14 ♂, HFHS n=8 ♀, n=7 ♂) followed by a novel object recognition task (NOR for intermediate memory; Con n=14 ♀, n=14 ♂, HFHS n=8 ♀, n=7 ♂). Behavioural data analysis used Two-way ANOVA with post hoc Sidak’s multiple comparison test or Unpaired t-test. Fetal and PN2 weights used a Linear mixed model repeated-measures ANOVA with mother as subject followed by post hoc Bonferroni t-test. Data expressed as mean or estimated marginal mean +SEM. At embryonic day 19 HFHS pups were growth restricted (Con 1.01±0.01g; HFHS 1.04±0.01g, p=0.0005) relative to controls, but not at PN2 (Con 1.48±0.04g vs HFHS 1.47±0.08g, p>0.05). Both male and female HFHS offspring displayed a deficit in intermediate memory showing no preference for the novel over the familiar object (discrimination index (DI) p<0.0001, Figure 1A). In the EPM task, HFHS offspring displayed reduced anxiety with increased entries (p=0.0053, Figure 1B) and time spent in the open arm (p=0.0066, Figure 1C). By 14 weeks of postnatal age, there were no differences in body weight, body fat percentage and brain weight between the control and HFHS offspring (p>0.05). This study has shown maternal obesity causes memory impairment and a reduction in anxiolytic behaviour in the offspring, despite eating a healthy balanced diet post-weaning and without any change in their adiposity, body or brain weight.
Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, C106
Oral Communications: Maternal obesity alters intermediate memory and anxiety-related behaviours inadult mouse offspring
E. J. Mort1, S. R. Heritage1, E. J. Camm1, A. L. Fowden1
1. Physiology Development & Neuroscience, University of Cambridge, Cambridge, United Kingdom.
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Figure 1: Behavioural results of 12 week old Control and HFHS offspring: (A) Discrimination index in the NOR task, (B) Entries into the open arm and (C) Duration in the open arm measures within the EPM task. *p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.
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