Chronostatic adaptations in the liver to restricted feeding: The FEO as an emergent oscillator

Abstract

We propose that the mammalian timing system is formed by constitutive clocks, such as the suprachiasmatic nucleus, and emerging clocks build up from the coordinated activity of peripheral oscillators, such as the food entrained oscillator (FEO). This timing system underlies a general regulatory process that modulates the set point of physiological variables in a periodic manner known as chronostasis. In contrast to the suprachiasmatic nucleus, the FEO is a distributed system formed by different brain areas such as the dorsomedial and ventromedial hypothalamus and the paraventricular thalamic nucleus, and peripheral organs such as the liver, adipose tissue, and skeletal muscle, and some endocrine glands. Central to the notion of FEO as an emerging oscillator is the establishment of a series of novel interactions between the molecular circadian clock and the biochemical events that coordinate the metabolic framework by which cellular energy is obtained, stored, and used. In the liver, those metabolic adaptations include changes in the handling of fatty acids, glycogenolysis, cytoplasmic and mitochondrial redox state, balance in the adenine nucleotides pool, intracellular calcium dynamics, and signaling from nuclear receptors. The paraventricular thalamic nucleus (PVT) integrates information from the circadian, feeding, and limbic systems, and thus is in a strategic position to convey different signals from the periphery related to the FEO into central areas related to overt circadian rhythms. The reconfiguration of the circadian system is an example of how biochemical, physiological, and behavioral processes are regulated by chronostasis to optimize the searching, assimilation, and processing of the nutrients during adverse environmental conditions.