Impact of perinatal exposure to high-fat diet and stress on responses to nutritional challenges, food-motivated behaviour and mesolimbic dopamine function

Background/Objectives: Energy-dense food exposure and stress during development have been suggested to contribute to obesity and metabolic disorders later in life. Although these factors are frequently associated, the effects of their combination have not yet been investigated. In this study, using an animal model, we examined the long-term impact of maternal high-fat diet (HFD) and early-life stress (ELS) on energy homoeostasis control and food motivation. Methods: Body weight growth under HFD, adipose tissue, body weight control in response to fasting and refeeding, food-motivated behaviour and mesolimbic dopamine function were examined in adult male offspring exposed to maternal HFD (during gestation and lactation) and/or ELS (maternal separation 3 h per day from postnatal day 2 to 14). Results: Maternal HFD or ELS alone had no significant effect on offspring body weight; however, the combination of these factors exacerbated body weight gain when animals were exposed to HFD after weaning. There are no other significant combinatory effects of these perinatal events. In contrast, independently of the maternal diet, ELS disrupted body weight control during a fasting–refeeding procedure, increased adipose tissue mass and altered lipid metabolism. Finally, maternal HFD and ELS both resulted in exacerbated food-motivated behaviour and blunted dopamine release in the nucleus accumbens during palatable food consumption. Conclusions: We report a synergistic effect of perinatal HFD exposure and stress on the susceptibility to gain weight under HFD. However, ELS has a stronger impact than maternal HFD exposure on energy homoeostasis and food motivation in adult offspring. Altogether, our results suggest a programming effect of stress and nutrition supporting the hypothesis of the developmental origin of health and disease.Environnement psychosocial précoce, empreintes biologiques et épigénétiques et état de santé à l'âge adulteIdEx Bordeau