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Maternal Western diet age-specifically alters female offspring voluntary physical activity and dopamine- and
Gregory N Ruegsegger1, Kolter B Grigsby1, Taylor J Kelty1
1Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
Insights
Maternal Western diet (WD) during pregnancy alters offspring physical activity. Female offspring showed age-specific changes in activity, linked to dopamine and leptin gene expression, but these effects were not passed to the next generation.
Area of Science:
- Reproductive biology
- Neuroscience
- Metabolic health
Background:
- Prenatal overnutrition, particularly from a Western diet (WD), is linked to developmental issues and increased obesity risk.
- Understanding the transgenerational impact of maternal diet on offspring behavior and metabolic health is crucial.
Purpose of the Study:
- To investigate the transgenerational effects of maternal WD consumption on offspring physical activity and associated neurobiological changes.
- To determine if maternal WD exposure influences dopamine and leptin pathways in offspring.
- To assess the role of ventral tegmental area (VTA) leptin signaling in mediating these effects.
Main Methods:
- Maternal Western diet (WD) exposure in mice.
- Assessment of voluntary wheel running activity in juvenile and adult F1 offspring (male and female).
- Analysis of dopamine receptor (DRD) and leptin (Lepr) gene expression in the nucleus accumbens (NAc) and VTA.
- Intra-VTA leptin antagonism using recombinant adeno-associated virus (rAAV).
- Evaluation of F2 offspring for physical activity and adiposity.
Main Results:
- F1 female offspring exhibited increased wheel running as juveniles but decreased activity as adults following maternal WD exposure.
- No significant differences in wheel running were observed in F1 male offspring.
- Altered DRD1, DRD2, and Lepr gene expression in the NAc and VTA correlated with activity changes in female offspring.
- Maternal WD increased body fat, leptin, and insulin in male, but not female, F1 offspring.
- VTA leptin antagonism affected wheel running in standard diet offspring but not in WD offspring.
Conclusions:
- Prenatal exposure to a Western diet induces age-specific alterations in voluntary physical activity in female offspring.
- These changes are associated with modifications in dopamine and leptin signaling pathways.
- The observed effects appear to be due to in utero somatic reprogramming rather than epigenetic inheritance.
- Ventral tegmental area leptin signaling plays a role in modulating physical activity in response to maternal diet.
Abstract:
Prenatal overnutrition affects development into adulthood and influences risk of obesity. We assessed the transgenerational effect of maternal Western diet (WD) consumption on offspring physical activity. Voluntary wheel running was increased in juvenile (4-7 wk of age), but decreased in adult (16-19 wk of age), F1 female WD offspring In contrast, no wheel-running differences in F1 male offspring were observed. Increased wheel running in juvenile female WD offspring was associated with up-regulated dopamine receptor (DRD)-1 and -2 in the nucleus accumbens (NAc) and with down-regulated Lepr in the ventral tegmental area (VTA). Conversely, decreased wheel running by adult female WD offspring was associated with down-regulated DRD1 in the NAc and with up-regulated Lepr in the VTA. Body fat, leptin, and insulin were increased in male, but not in female, F1 WD offspring. Recombinant virus (rAAV) leptin antagonism in the VTA decreased wheel running in standard diet but not in WD F1 female offspring. Analysis of F2 offspring found no differences in wheel running or adiposity in male or female offspring, suggesting that changes in the F1 generation were related to in utero somatic reprogramming. Our findings indicate prenatal WD exposure leads to age-specific changes in voluntary physical activity in female offspring that are differentially influenced by VTA leptin antagonism.-Ruegsegger, G. N., Grigsby, K. B., Kelty, T. J., Zidon, T. M., Childs, T. E., Vieira-Potter, V. J., Klinkebiel, D. L., Matheny, M., Scarpace, P. J., Booth, F. W. Maternal Western diet age-specifically alters female offspring voluntary physical activity and dopamine- and leptin-related gene expression.
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