Maternal Western diet age‐specifically alters female offspring voluntary physical activity and dopamine‐ and leptin‐related gene expression

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 <i>Lepr</i> 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 <i>Lepr</i> 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 <i>in utero</i> 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.