Fat intake, stress responses and endocannabinoids in neonatal development

已知高脂肪饮食在包括糖尿病、肥胖症和心血管疾病在内的几种病理学的发展中至关重要。喂食高脂肪食物通常会导致内源性“应激”激素皮质醇的产生增加，皮质醇在高水平时会损害几种外周和中枢脑功能。然而，在出生后断奶前的一段时间里，母鼠的高脂肪乳汁会减少而不是增加应激激素的产生，这种特殊情况可以帮助我们了解如何保护大脑免受成年期高脂肪饮食的影响。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），类似于大麻的活性成分。 这些eCB在压力源作用后分泌，专门减少大脑中的压力反应。在这项提议中，我们测试了一个假设，即高脂肪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产生的治疗干预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.