Gangitano Elena, Gnessi Lucio, Lenzi Andrea, Ray David
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
Front Neurosci. 2021 Nov 8;15:756970. doi: 10.3389/fnins.2021.756970. eCollection 2021.
Circadian rhythms underpin most physiological processes, including energy metabolism. The core circadian clock consists of a transcription-translation negative feedback loop, and is synchronized to light-dark cycles by virtue of light input from the retina, to the central clock in the suprachiasmatic nucleus in the hypothalamus. All cells in the body have circadian oscillators which are entrained to the central clock by neural and humoral signals. In addition to light entrainment of the central clock in the brain, it now emerges that other stimuli can drive circadian clock function in peripheral tissues, the major one being food. This can then drive the liver clock to be misaligned with the central brain clock, a situation of internal misalignment with metabolic disease consequences. Such misalignment is prevalent, with shift workers making up 20% of the working population. The effects of diet composition on the clock are not completely clarified yet. High-fat diet and fasting influence circadian expression of clock genes, inducing phase-advance and phase-delay in animal models. Ketogenic diet (KD) is able to induce a metabolic switch from carbohydrate to fatty acid oxidation, miming a fasting state. In recent years, some animal studies have been conducted to investigate the ability of the KD to modify circadian gene expression, and demonstrated that the KD alters circadian rhythm and induces a rearrangement of metabolic gene expression. These findings may lead to new approaches to obesity and metabolic pathologies treatment.
昼夜节律是大多数生理过程的基础，包括能量代谢。核心昼夜节律时钟由一个转录 - 翻译负反馈环组成，并通过视网膜的光输入与下丘脑视交叉上核中的中央时钟同步，从而与明暗周期同步。体内所有细胞都有昼夜节律振荡器，它们通过神经和体液信号与中央时钟同步。除了大脑中中央时钟的光同步外，现在发现其他刺激也可以驱动外周组织中的昼夜节律时钟功能，其中主要的刺激是食物。这进而会导致肝脏时钟与大脑中央时钟失调，这种内部失调的情况会产生代谢疾病后果。这种失调很普遍，轮班工作者占劳动人口的20%。饮食成分对生物钟的影响尚未完全阐明。高脂肪饮食和禁食会影响生物钟基因的昼夜表达，在动物模型中诱导相位提前和相位延迟。生酮饮食（KD）能够诱导从碳水化合物氧化到脂肪酸氧化的代谢转变，模拟禁食状态。近年来，已经进行了一些动物研究来调查生酮饮食改变昼夜节律基因表达的能力，并证明生酮饮食会改变昼夜节律并诱导代谢基因表达的重新排列。这些发现可能会带来治疗肥胖和代谢疾病的新方法。
