Caloric restriction and the developing brain

Abstract Caloric restriction (CR) is the reduction of calorie intake, taking care of the micronutrient supplementation. Alternatively, if vitamins and minerals are not complemented in the restricted diet, we call it food restriction (FR). CR is the main way to increase life span and to prevent several nontransmissible chronic diseases. It has been studied in adult humans and animals, where some of the mechanisms by which CR acts have been elucidating, including the activation of peroxisome proliferator–activated receptors, AMP-activated protein kinase, sirtuins, nuclear factor erythroid 2-related factor 2, forkhead box proteins, the inhibition of nuclear factor-κB, mechanistic target of rapamycin, and insulin-like growth factor 1/phosphoinositide 3-kinase/AKT pathway. In addition, epigenetic targets such as DNA methylation, histone covalent modifications, and microRNAs are also regulated by CR, allowing the long-term effects of this dietetic intervention. In this sense, CR, when applied during pregnancy, modulates the metabolism of the next generation. The sparse literature shows that maternal CR, applied during pregnancy, increases the antioxidant network and reduces the oxidative stress in several brain areas from offspring. On the other hand, FR, when applied prenatally, in general has a negative impact on the progeny, altering the redox status, inhibiting the endocannabinoid system, altering leptin and insulin signaling, shifting the satiety neurons in hypothalamus, and impairing memory. Considering the results found in animal models is essential to control the diet during pregnancy avoiding a negative metabolic impact on the next generation, reverberating in a long-term way.