bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2020‒02‒16
six papers selected by
Gabriela Da Silva Xavier
University of Birmingham


  1. F1000Res. 2020 ;pii: F1000 Faculty Rev-51. [Epub ahead of print]9
    Hearn TJ, Webb AAR.
      Circadian clocks have evolved to synchronise an organism's physiology with the environmental rhythms driven by the Earth's rotation on its axis. Over the past two decades, many of the genetic components of the Arabidopsis thaliana circadian oscillator have been identified. The interactions between these components have been formulized into mathematical models that describe the transcriptional translational feedback loops of the oscillator. More recently, focus has turned to the regulation and functions of the circadian clock. These studies have shown that the system dynamically responds to environmental signals and small molecules. We describe advances that have been made in discovering the cellular mechanisms by which signals regulate the circadian oscillator of Arabidopsis in the context of tissue-specific regulation.
    Keywords:  Arabidopsis; Circadian; cellular; dynamic; regulator
    DOI:  https://doi.org/10.12688/f1000research.21307.1
  2. Sci Rep. 2020 Feb 13. 10(1): 2569
    Inokawa H, Umemura Y, Shimba A, Kawakami E, Koike N, Tsuchiya Y, Ohashi M, Minami Y, Cui G, Asahi T, Ono R, Sasawaki Y, Konishi E, Yoo SH, Chen Z, Teramukai S, Ikuta K, Yagita K.
      Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms, which showed that long-term circadian misalignment induced significant early mortality. Non-biased RNA sequencing analysis using liver and kidney showed marked activation of gene regulatory pathways associated with the immune system and immune disease in both organs. In accordance, we observed enhanced steatohepatitis with infiltration of inflammatory cells. The investigation of senescence-associated immune cell subsets from the spleens and mesenteric lymph nodes revealed an increase in PD-1+CD44high CD4 T cells as well as CD95+GL7+ germinal center B cells, indicating that the long-term circadian misalignment exacerbates immune senescence and consequent chronic inflammation. Our results underscore immune homeostasis as a pivotal interventional target against clock-related disorders.
    DOI:  https://doi.org/10.1038/s41598-020-59541-y
  3. F1000Res. 2020 ;pii: F1000 Faculty Rev-61. [Epub ahead of print]9
    Mistlberger RE.
      Feeding schedules entrain circadian clocks in multiple brain regions and most peripheral organs and tissues, thereby synchronizing daily rhythms of foraging behavior and physiology with times of day when food is most likely to be found. Entrainment of peripheral clocks to mealtime is accomplished by multiple feeding-related signals, including absorbed nutrients and metabolic hormones, acting in parallel or in series in a tissue-specific fashion. Less is known about the signals that synchronize circadian clocks in the brain with feeding time, some of which are presumed to generate the circadian rhythms of food-anticipatory activity that emerge when food is restricted to a fixed daily mealtime. In this commentary, I consider the possibility that food-anticipatory activity rhythms are driven or entrained by circulating ghrelin, ketone bodies or insulin. While evidence supports the potential of these signals to participate in the induction or amount of food-anticipatory behavior, it falls short of establishing either a necessary or sufficient role or accounting for circadian properties of anticipatory rhythms. The availability of multiple, circulating signals by which circadian oscillators in many brain regions might entrain to mealtime has supported a view that food-anticipatory rhythms of behavior are mediated by a broadly distributed system of clocks. The evidence, however, does not rule out the possibility that multiple peripheral and central food-entrained oscillators and feeding-related signals converge on circadian oscillators in a defined location which ultimately set the phase and gate the expression of anticipatory activity rhythms. A candidate location is the dorsal striatum, a core component of the neural system which mediates reward, motivation and action and which contains circadian oscillators entrainable by food and dopaminergic drugs. Systemic metabolic signals, such as ghrelin, ketones and insulin, may participate in circadian food anticipation to the extent that they modulate dopamine afferents to circadian clocks in this area.
    Keywords:  anticipatory activity; circadian; dopamine; entrainment; food; ghrelin; insulin; ketone; reward
    DOI:  https://doi.org/10.12688/f1000research.20829.1
  4. Science. 2020 Feb 14. 367(6479): 800-806
    Ray S, Valekunja UK, Stangherlin A, Howell SA, Snijders AP, Damodaran G, Reddy AB.
      Circadian (~24 hour) clocks have a fundamental role in regulating daily physiology. The transcription factor BMAL1 is a principal driver of a molecular clock in mammals. Bmal1 deletion abolishes 24-hour activity patterning, one measure of clock output. We determined whether Bmal1 function is necessary for daily molecular oscillations in skin fibroblasts and liver slices. Unexpectedly, in Bmal1 knockout mice, both tissues exhibited 24-hour oscillations of the transcriptome, proteome, and phosphoproteome over 2 to 3 days in the absence of any exogenous drivers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. We suggest that such oscillations might be underpinned by transcriptional regulation by the recruitment of ETS family transcription factors, and nontranscriptionally by co-opting redox oscillations.
    DOI:  https://doi.org/10.1126/science.aaw7365
  5. Nat Rev Endocrinol. 2020 Feb 13.
    Lewis P, Oster H, Korf HW, Foster RG, Erren TC.
      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.
    DOI:  https://doi.org/10.1038/s41574-020-0318-z
  6. J Endocrinol. 2020 Feb 01. pii: JOE-20-0011. [Epub ahead of print]
    Segers A, Desmet L, Sun S, Verbeke K, Tack J, Depoortere I.
      The known crosstalk between short-chain fatty acids (SCFAs) and the circadian clock is tightly intertwined with feeding time. We aimed to investigate the role of the core clock gene Bmal1 and feeding time in the diurnal rhythms in plasma and caecal SCFAs levels and in their effect on the release of the hunger hormone ghrelin in the stomach and colon. WT, Bmal1-/- (ad libitum fed) and night-time-restricted-fed (RF)-Bmal1-/-- littermates were sacrificed at Zeitgeber time (ZT) 4 and 16. SCFA concentrations were measured by gas chromatography. To investigate the effect of SCFAs on ghrelin release, stomach and colonic full-thickness strips were incubated with Krebs or a SCFA mix mimicking plasma or caecal concentrations, after which octanoyl ghrelin release was measured by radioimmunoassay. Diurnal rhythms in caecal and plasma SCFAs oscillated in phase but rhythmic changes were abolished in Bmal1-/- mice. RF of Bmal1-/- mice restored fluctuations in caecal SCFAs. Plasma SCFA concentrations failed to affect gastric ghrelin release. The effect of caecal SCFA concentrations on colonic ghrelin release was rhythmic (inhibition at ZT 4, no effect at ZT 16). In Bmal1-/- mice, the inhibitory effect of SCFAs at ZT 4 was abolished. RF Bmal1-/- mice restored the inhibitory effect and increased colonic Clock expression. To conclude, diurnal fluctuations in caecal SCFAs and the effect of SCFAs on colonic ghrelin release are regulated by feeding time, independent of the core clock gene BMAL1. However, local entrainment of other clock genes might contribute to the observed effects.
    DOI:  https://doi.org/10.1530/JOE-20-0011