“Feeding time” for the brain: A matter of clocks

Abstract

Circadian clocks are autonomous time-keeping mechanisms that allow living organisms to predict and adapt to environmental rhythms of light, temperature and food availability. At the molecular level, circadian clocks use clock and clock-controlled genes to generate rhythmicity and distribute temporal signals. In mammals, synchronization of the master circadian clock located in the suprachiasmatic nuclei of the hypothalamus is accomplished mainly by light stimuli. Meal time, that can be experimentally modulated by temporal restricted feeding, is a potent synchronizer for peripheral oscillators with no clear synchronizing influence on the suprachiasmatic clock. Furthermore, food-restricted animals are able to predict meal time, as revealed by anticipatory bouts of locomotor activity, body temperature and plasma corticosterone. These food anticipatory rhythms have long been thought to be under the control of a food-entrainable clock (FEC). Analysis of clock mutant mice has highlighted the relevance of some, but not all of the clock genes for foodentrainable clockwork. Mutations of Clock or Per1 do not impair expression of food anticipatory components, suggesting that these clock genes are not essential for food-entrainable oscillations. By contrast, mice mutant for Npas2 or deficient for Cry1 and Cry2 show more or less altered responses to restricted feeding conditions. Moreover, a lack of food anticipation is specifically associated with a mutation of Per2, demonstrating the critical involvement of this gene in the anticipation of meal time. The actual location of the FEC is not yet clearly defined. Nevertheless, current knowledge of the putative brain regions involved in food-entrainable oscillations is discussed. We also describe several neurochemical pathways, including orexinergic and noradrenergic, likely to participate in conveying inputs to and outputs from the FEC to control anticipatory processes.

Transcriptional Repressor E4-binding Protein 4 (E4BP4) Regulates Metabolic Hormone Fibroblast Growth Factor 21 (FGF21) during Circadian Cycles and Feeding

“…Feeding Suppresses FGF21 Expression through Up-regulating E4BP4-Circadian rhythms control the daily cycle of feeding and fasting (2)(3)(4)47). The Fgf21 mRNA is significantly induced by fasting but potently repressed by feeding (35,36).…”

“…Two major components of the circadian network, ROR␣ (retinoic acid receptor-related receptor ␣) and Rev-erb␣, have also been found to regulate FGF21 expression (43,44). Given that FGF21 expression is sensitive to the feeding state (45)(46)(47), we speculate that the FGF21 level oscillates during a circadian * This work was supported, in whole or in part, by National Institutes of Health cycle, which is intimately coupled with a feeding and fasting cycle.…”

Bile Acid-regulated Peroxisome Proliferator-activated Receptor-α (PPARα) Activity Underlies Circadian Expression of Intestinal Peptide Absorption Transporter PepT1/Slc15a1

“…Although the light/dark cycle is the most powerful "Zeitgeber" for the suprachiasmatic nucleus oscillators in mammals (17,18), feeding regimen is also important for the generation and synchronization of peripheral circadian rhythms (19). The intestinal expressions of Slc15a1/PepT1 are induced by situations of fasting or starvation (20).…”

Circadian variations in blood pressure in health and disease: implications for patient management

“…This light-sensitive entrainment of the suprachiasmatic nuclei is not universally accepted as the only major impetus for synchronization of diurnal variations in mammalian physiological processes. [22][23][24] Furthermore, the discovery of autonomous oscillators in other regions of the mammalian brain and peripheral tissues challenges the paradigm that there is only one major clock coordinating biological rhythms. 25 However, for the purpose of this discussion we will focus on the suprachiasmatic nuclei as the central clock, synchronized each day by exposure to light, coordinating rhythmic variations in physiological function.…”