Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy.
Institute of Clinical Physiology, National Research Council (CNR), 56124 Pisa, Italy.
Nutrients. 2022 Mar 17;14(6):1275. doi: 10.3390/nu14061275.
We are facing an obesity epidemic, and obesity itself and its close companion, type 2 diabetes, are independent risk factors for neurodegeneration. While most medical treatments fail to induce a clinically meaningful improvement in neurodegenerative disorders, lifestyle interventions have emerged in the spotlight. A recently rediscovered approach is intermittent fasting (IF), which, compared to the classic caloric restriction regimens, limits only the time of eating, rather than the number of calories allowed per day. There is already a large amount of evidence from preclinical and clinical studies showing the beneficial effects of IF. In this review, we specifically focus on the effects of IF on brain metabolism. Key molecular players modified during IF and involved in its beneficial central effects (ketone bodies, BDNF, GABA, GH/IGF-1, FGF2, sirtuin-3, mTOR, and gut microbiota) are identified and discussed. Studies suggest that IF induces several molecular and cellular adaptations in neurons, which, overall, enhance cellular stress resistance, synaptic plasticity, and neurogenesis. Still, the absence of guidelines regarding the application of IF to patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge on the different IF protocols and long-term effects of IF on brain metabolism before it can be widely prescribed.
我们正面临着肥胖症的流行，肥胖症及其密切相关的 2 型糖尿病本身就是神经退行性疾病的独立危险因素。虽然大多数医学治疗都未能在神经退行性疾病中诱导出有临床意义的改善，但生活方式干预已成为关注焦点。一种最近重新发现的方法是间歇性禁食（IF），与经典的热量限制方案相比，IF 只限制进食时间，而不是每天允许的卡路里数量。已经有大量来自临床前和临床研究的证据表明 IF 的有益效果。在这篇综述中，我们特别关注 IF 对大脑代谢的影响。在 IF 期间被修饰并参与其有益的中枢作用的关键分子参与者（酮体、BDNF、GABA、GH/IGF-1、FGF2、sirtuin-3、mTOR 和肠道微生物群）被识别和讨论。研究表明，IF 诱导神经元发生几种分子和细胞适应性，总体上增强了细胞应激抗性、突触可塑性和神经发生。尽管关于将 IF 应用于患者的指南尚未确定，这限制了其在临床实践中的广泛应用，但仍需要进一步的研究来提高我们对不同 IF 方案和 IF 对大脑代谢的长期影响的认识，然后才能广泛应用。
