Abstract
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.
Highlights
The Clock Machinery and the Circadian RhythmIn mammalians many genes exhibit daily fluctuations in their expression levels, configuring a circadian rhythm of approximately 24 h
At a cellular level the circadian clock is constituted by core clock genes, including CLOCK, BMAL1, PER, and CRY, that are connected by transcriptional-translational feedback loops (Albrecht, 2012)
The effects of a ketogenic diet on clock gene expression have been recently investigated in mouse models, and these studies showed that Ketogenic diet (KD) is able to influence circadian rhythm
Summary
In mammalians many genes exhibit daily fluctuations in their expression levels, configuring a circadian rhythm of approximately 24 h This circadian oscillation is internally generated (Ko and Takahashi, 2006; Dibner et al, 2010) and driven by clock machinery. At a cellular level the circadian clock is constituted by core clock genes, including CLOCK, BMAL1, PER, and CRY, that are connected by transcriptional-translational feedback loops (Albrecht, 2012). The clock machinery controls physiology processes by regulating the expression of hundreds of metabolic genes, involved in the rate-limiting steps of fundamental metabolic pathways It orchestrates metabolism in cycles of 24 h, and increases metabolic efficiency thanks to anticipatory responses to the feeding-fasting cycles and temporal separation of opposite metabolic processes (Panda, 2016; Poggiogalle et al, 2018; Reinke and Asher, 2019). The SCN-liver axis for circadian rhythm is probably the most important connection between the central clock and the peripheral clocks
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