Fat intake, stress responses and endocannabinoids in neonatal development

众所周知，高脂肪饮食在糖尿病、肥胖症和心血管疾病等几种疾病的发展中起着至关重要的作用。喂食高脂肪食物通常会导致内源性“应激”荷尔蒙皮质醇的产生增加，这种荷尔蒙在高水平时会损害几种外周和中枢大脑功能。然而，在幼鼠断奶前的出生后阶段，母亲的高脂牛奶会减少而不是增加压力荷尔蒙的产生，这种特殊的情况可以帮助我们理解如何在成年后保护大脑不受高脂肪饮食的影响。饮食中的特定脂肪可以作为大脑递质的前体，称为内源性大麻素(ECB)，它类似于大麻的活性成分。这些ECB是在应激源作用后分泌出来的，专门减少大脑中的应激反应。在这项建议中，我们测试了这样的假设，即高脂牛奶对发育中的幼崽的应激反应具有保护作用，因为它增强了大脑内源性大麻素的产生和分泌。旨在增加成人ECB产量的治疗干预措施可能会减少应激激素对疾病发展的负面影响。

High fat diets are known to be critical in the development of several pathologies including diabetes, obesity and cardiovascular diseases. Feeding on high fat diets usually results in an increased production of the endogenous "stress" hormone cortisol, which at high levels, impairs several peripheral and central brain functions. However, during the postnatal period prior to weaning in rat pups, high fat milk from the mother reduces, rather than enhances stress hormones production and this particular situation could help us understand how to protect the brain from high fat diets in adulthood. Specific fats in the diet can act as precursors for brain transmitters called endocannabinoids (eCBs), which are analogous to the active component of marijuana.  These eCBs, secreted following a stressor act to specifically reduce stress responses in the brain. In this proposal, we test the hypothesis that high fat milk is protective to stress responses in developing pups because it enhances the production and secretion of brain endocannabinoids. Therapeutic interventions aimed at increasing eCBs production in adults might allow to reduce the negative effects of stress hormones on the development of disease.