During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease.

在进化过程中，大脑和身体在禁食状态下运作良好的个体成功地获取了食物，从而得以生存和繁殖。随着禁食和长期运动，肝脏糖原的储存被消耗掉，而脂肪细胞衍生的脂肪酸产生了酮。细胞燃料来源的这种新陈代谢转换伴随着大脑神经网络的细胞和分子适应，从而增强了它们的功能并增强了它们对压力，伤害和疾病的抵抗力。在这里，我们考虑间歇性的新陈代谢转换，新陈代谢挑战的重复循环（诱发空腹（禁食和/或运动），然后是恢复期（进食，休息和睡觉））如何在整个生命周期内优化大脑功能和弹性，重点关注与认知和情绪有关的神经元回路。这种代谢转换影响多种信号通路，从而促进神经可塑性和大脑对损伤和疾病的抵抗力。