Food as a circadian time cue - evidence from human studies.

Meal timing and composition are frequently reported in the literature as zeitgebers (that is, time cues) for the circadian system of humans and animal models, albeit secondary to light. Although widely assumed to be true, evidence for food zeitgeber effects specific to humans is notably scarce. Fostering zeitgeber hygiene in the general population as the development and practice of healthy use of zeitgebers could potentially reduce chronobiological strain, which is defined as disruption or misalignment within the circadian system. Such chronobiological strain is associated with modern 24/7 lifestyles (for example, shift work) and several negative health outcomes. Adjustments to meal timing and composition are an attractive strategy to synchronize circadian rhythms and develop zeitgeber hygiene. Thus, clarifying the actual effect of meal timing and composition on the human circadian system is a crucial piece of the human chronobiology puzzle. This Review weighs the evidence from human studies pertaining to the hypothesis that food is a circadian zeitgeber by comparing findings against formal zeitgeber criteria put forward by Jürgen Aschoff in the 1950s.

Exercise time cues (zeitgebers) for human circadian systems can foster health and improve performance: a systematic review.

BACKGROUND: Circadian system time cues (zeitgebers) acting synergistically at the right times can foster chronobiological homeostasis and ultimately health. Modern 24/7 societies are challenging chronobiological homeostasis and public health. Exercise has been discussed as a potential zeitgeber for the human circadian system. Thus, if timed correctly, exercise may help in maintenance of chronobiological homeostasis and foster public health amidst increasingly challenging 24/7 lifestyles. OBJECTIVE: To test, using a systematic review of the literature, the following hypothesis: exercise is a zeitgeber for the human circadian system. DATA SOURCES: The PubMed database was systematically searched on 19 October 2017 for relevant scientific studies and reports concerning chronobiology and exercise. Eligibility criteria were defined to include articles considering exercise as a potential zeitgeber for human circadian rhythmicity or chronobiological effects of exercise on health and/or physical performance. Cognitive effects and effects on children were excluded from the synthesis. RESULTS: Our systematic literature search and synthesis is compatible with the validity of the hypothesis. We report that potential exercise-zeitgeber properties may be used to improve health and performance. CONCLUSIONS: Informed timing of exercise, specific to the circadian rhythm phase and zeitgeber exposure of the individual, must be advocated in performance and disease contexts as an adjunct therapeutic or preventative strategy and physical enhancer.

Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice.

In young (35- to 56-day-old) and middle-aged (9-mo-old) wild-type (+/+) and melanocortin-4 receptor (MC4R)-deficient (+/-, -/-) mice, expressions of neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin (POMC), and cocaine-and-amphetamine-regulated transcript (CART) were analyzed in the arcuate nucleus (ARC) and adjacent regions comprising the dorsomedial (DMN) and ventromedial (VMN) nucleus. In the ARC of young mice, NPY and AGRP expression increased and POMC and CART expression decreased with body fat content. Adjusting for the influence of body fat content by ANCOVA showed that the levels of NPY, POMC, and CART were highest and of AGRP lowest in young -/- mice. In the middle-aged mice, feedback from body fat content was weakened. For -/- mice ANCOVA revealed higher NPY and AGRP, lower POMC, and unchanged CART expression levels relative to young -/- mice. In the DMN and VMN, POMC and AGRP signals were absent at each age. CART was expressed in the DMN independent of age, fat content, and genotype. For NPY expression, an age-dependent induction was found in the DMN and VMN; it was absent in the young but present in the middle-aged mice, showing close positive correlations between body fat content and the numbers of NPY-labeled cells which were further enhanced in -/- mice. Thus MC4R deficiency augments age-induced NPY expression in the DMN and VMN with no feedback from body fat content. Negative feedback control by body fat content on ARC neuropeptide expression is present in young animals but vanishes with age and is modulated by MC4R deficiency.

Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock.

Biological rhythms are driven in mammals by a central circadian clock located in the suprachiasmatic nucleus (SCN). Light-induced phase shifting of this clock is correlated with phosphorylation of CREB at Ser133 in the SCN. Here, we characterize phosphorylation of CREB at Ser142 and describe its contribution to the entrainment of the clock. In the SCN, light and glutamate strongly induce CREB Ser142 phosphorylation. To determine the physiological relevance of phosphorylation at Ser142, we generated a mouse mutant, CREB(S142A), lacking this phosphorylation site. Light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN are significantly attenuated in CREB(S142A) mutants. Our findings provide genetic evidence that CREB Ser142 phosphorylation is involved in the entrainment of the mammalian clock and reveal a novel phosphorylation-dependent regulation of CREB activity.