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), F female WD offspring In contrast, no wheel-running differences in F 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 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 in the VTA. Body fat, leptin, and insulin were increased in male, but not in female, F WD offspring. Recombinant virus (rAAV) leptin antagonism in the VTA decreased wheel running in standard diet but not in WD F female offspring. Analysis of F offspring found no differences in wheel running or adiposity in male or female offspring, suggesting that changes in the F generation were related to 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.

Fetal brain and placental programming in maternal obesity: A review of human and animal model studies

“…66 Maternal Western diet during pregnancy was associated with increased locomotor activity in juvenile female offspring, while adult female, but not male, offspring demonstrated decreased locomotor activity. 69 to controls, consistent with increased anxiety. [71][72][73][74][75][76][77] Anxiety-like behavior in offspring of obese dams has also been noted in the morris water maze task, open field test, and light-dark transition tests.…”

“…Rodent studies have shown increased locomotor activity in the offspring of obese dams, although data are conflicting regarding which sex is more affected by this exposure. 66,69,70 Male offspring exposed to a maternal HFD demonstrated increased hyperactivity in the open field test, which was not corrected by maternal dietary intervention during lactation. 66 Maternal Western diet during pregnancy was associated with increased locomotor activity in juvenile female offspring, while adult female, but not male, offspring demonstrated decreased locomotor activity.…”

“…133,135 As previously described, animal studies have demonstrated that male and female offspring show different neurodevelopmental susceptibilities in the setting of maternal obesity. 66,67,[69][70][71]79,96 Human placenta studies suggest that maternal obesity affects oxidative stress and antioxidant activity in a sexually dimorphic manner, with male placentas demonstrating a more significant reduction in antioxidant capacity than females, and a significant upregulation in the activity of the antioxidant selenoprotein enzymes, glutathione peroxidase and thioredoxin reductase. 173…”

The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease

“…Epigenetics, such as DNA methylation, may be involved in the impact the western diet has on the human body. The effects of maternal Western diet on offspring physical activity, gene expression, and phenotype were assessed in [ 44 ]. Interestingly, differences in F1 female offspring but not in F2 male and female offspring were observed, suggesting that changes in the F1 generation were related to in utero somatic reprogramming.…”

The role of nucleus accumbens CREB attenuation in rescuing low voluntary running behavior in female rats

“…To determine the role of reducing NAc neuronal activity on voluntary wheel-running behavior in an inducible fashion, a separate set of TA B L E 1 Listing of primary antibodies used have been successfully used in our laboratory (Grigsby et al, 2018;Ruegsegger et al, 2017). Following injections, incisions were closed using tissue adhesive (Vetbond, 3M, Maplewood, MN), and rats were allowed to recover on a 32°C heating pad until ambulatory.…”