Maternal obesity in the rat programs male offspring exploratory, learning and motivation behavior: prevention by dietary intervention pre‐gestation or in gestation

Abstract

We studied the effects of maternal high fat diet (HFD, 25% calories from fat administered before and during pregnancy and lactation) and dietary intervention (switching dams from HFD to control diet) at different periconceptional periods on male offspring anxiety related behavior, exploration, learning, and motivation. From weaning at postnatal day (PND) 21, female subjects produced to be the mothers in the study received either control diet (CTR - 5% calories from fat), HFD through pregnancy and lactation (MO), HFD during PNDs 21-90 followed by CTR diet (pre-gestation (PG) intervention) or HFD from PND 21 to 120 followed by CTR diet (gestation and lactation (G) intervention) and bred at PND 120. At 19 days of gestation maternal serum corticosterone was increased in MO and the PG and G dams showed partial recovery with intermediate levels. In offspring, no effects were found in the elevated plus maze test. In the open field test, MO and G offspring showed increase zone entries, displaying less thigmotaxis; PG offspring showed partial recuperation of this behavior. During initial operant conditioning MO, PG and G offspring displayed decreased approach behavior with subsequent learning impairment during the acquisition of FR-1 and FR-5 operant conditioning for sucrose reinforcement. Motivation during the progressive ratio test increased in MO offspring; PG and G intervention recuperated this behavior. We conclude that dietary intervention can reverse negative effects of maternal HFD and offspring outcomes are potentially due to elevated maternal corticosterone.

Aging, glucocorticoids and developmental programming

“…We standardized the study subjects to remove disease-related confounds of the aging process. All animals were from our wellcharacterized colony of healthy male and female rats that has been maintained for several generations in standard conditions (Rodriguez et al 2012;Vega et al 2015;Zambrano et al 2010). Background patrilineal and matrilineal data were available from all subjects to ensure homogeneity and lack of siblings among F 0 mothers in different studies.…”

“…Glucocorticoids play a critical role during gestation in maturing a variety of fetal organs by stimulating differentiation and inhibiting growth and proliferation. We have previously published Rodriguez et al 2012;Vega et al 2015;Zambrano and Nathanielsz 2013) that a, e Represent a normal; b, f a premature; c, g an augmented; and d, h a premature and augmented aging process maternal serum corticosterone concentrations in maternal obesity (MO) were higher than controls (C) at the time of breeding, end of gestation, 19 days gestation (dG), and end of lactation, postnatal day (PND) 21. Prenatal exposure to increased levels of glucocorticoids changes hypothalamic pituitary adrenal axis function (Braun et al 2013).…”

Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions

“…This may be due to an increased preference for these macronutrients (Vucetic et al, 2010) but is not associated with altered orosensory stimulation by their taste (Treesukosol et al, 2014). Whilst food preferences can be programmed by maternal nutrition (reviewed in (Gugusheff et al, 2014)), maternal obesity is also associated with altered motivation for palatable foods in multiple rodent models (Grissom et al, 2014b;Naef et al, 2011;Rodriguez et al, 2012). The programmed increases in preference for fat and sugar and altered motivation to work for such foods are associated with changes in dopaminergic tone (Naef et al, 2011(Naef et al, , 2013 as well as in expression of key dopaminergic and opioidergic signalling genes (Naef et al, 2011;Ong and Muhlhausler, 2011;Vucetic et al, 2010), with evidence for epigenetic regulation at some loci (Grissom et al, 2014a;Vucetic et al, 2010).…”

“…Dietary intervention from before pregnancy or during lactation normalises the increased adiposity and circulating leptin, insulin and triglycerides in weanling offspring, rescues the altered motivation and hyperphagia and partially normalises glucose homeostasis and adipocyte morphology in adulthood (Bayol et al, 2007;Rodriguez et al, 2012;Zambrano et al, 2010). In addition, maternal dietary intervention rescues the increased anxiety and altered social behaviours in female offspring of maternal DIO mice in association with amelioration of central inflammation in these offspring (Kang et al, 2014).…”

Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats

“…Maternal over nutrition and obesity during pregnancy and/or lactation affects offspring metabolic phenotype (56), cardiovascular function (46), anxiety behavior, associative learning, and motivation (36). In contrast, programming of offspring reproductive capacity by maternal obesity is poorly documented.…”