bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2021‒04‒25
eight papers selected by
Gabriela Da Silva Xavier
University of Birmingham

  1. Curr Opin Clin Nutr Metab Care. 2021 Apr 20.
      PURPOSE OF REVIEW: Glucose metabolism is under circadian regulation, with insulin secretion and sensitivity being highest in the morning as compared to the evening. The present review will discuss the existing evidence for the role of meal and macronutrient timing to improve glucose metabolism and reset circadian clocks, with a focus on the evidence in humans.RECENT FINDINGS: Shortening the daily eating window (also known as time-restricted eating), or skewing food intake towards breakfast and away from the evening meal both improve glucose control in people with impaired glucose metabolism. Insulin is recently purported to be a zeitgeber and thus an important reset signal for peripheral circadian clocks in vitro and in mice. Although few studies have tested the impact of macronutrient timing in humans, eating a greater proportion of carbohydrates earlier, rather than later, in the day is associated with better glucose control.
    SUMMARY: The impact of carbohydrate intake timing on endogenous central and peripheral clocks, and its potential to optimize circadian regulation and improve glycaemic control, are not well understood but are currently under intense exploration.
  2. Nat Commun. 2021 Apr 22. 12(1): 2388
      To unravel the pathogenesis of obesity and its complications, we investigate the interplay between circadian clocks and NF-κB pathway in human adipose tissue. The circadian clock function is impaired in omental fat from obese patients. ChIP-seq analyses reveal that the core clock activator, BMAL1 binds to several thousand target genes. NF-κB competes with BMAL1 for transcriptional control of some targets and overall, BMAL1 chromatin binding occurs in close proximity to NF-κB consensus motifs. Obesity relocalizes BMAL1 occupancy genome-wide in human omental fat, thereby altering the transcription of numerous target genes involved in metabolic inflammation and adipose tissue remodeling. Eventually, clock dysfunction appears at early stages of obesity in mice and is corrected, together with impaired metabolism, by NF-κB inhibition. Collectively, our results reveal a relationship between NF-κB and the molecular clock in adipose tissue, which may contribute to obesity-related complications.
  3. FASEB J. 2021 May;35(5): e21590
      Light is the key regulator of circadian clock, the time-keeping system synchronizing organism physiology and behavior with environmental day and night conditions. In its natural habitat, the strictly subterranean naked mole-rat (Heterocephalus glaber) has lived in a light-free environment for millennia. We questioned if this species retains a circadian clock and if the patterns of this clock and concomitant rhythms differed in liver tissue from mice and naked mole-rats. As expected, in mice, the various circadian clock genes peaked at different times of the day; the Period gene (Per) group peaked in the evening, whereas Brain and Muscle ARNT-like1 (Bmal1) gene peaked in the morning; this phase shift is considered to be fundamental for circadian clock function. In sharp contrast, in the naked mole-rat both Per1 and Per2, as well as Bmal1, peaked at the same time in the morning-around ZT2-suggesting the organization of the molecular circadian oscillator was different. Moreover, gene expression rhythms associated with glucose metabolism and mTOR signaling also differed between the species. Although the activity of mTORC1 was lower, while that of mTORC2 was higher in naked mole-rat livers compared to mice, unlike that of mice where the expression profiles of glucose metabolism genes were not synchronized, these were highly synchronized in naked mole-rats and likely linked to their use of feeding times at zeitgebers.
    Keywords:  aging; circadian rhythms; clock; glucose metabolism; longevity; mTOR; naked mole-rat
  4. Genes Dev. 2021 Apr 22.
      Mammals undergo regular cycles of fasting and feeding that engage dynamic transcriptional responses in metabolic tissues. Here we review advances in our understanding of the gene regulatory networks that contribute to hepatic responses to fasting and feeding. The advent of sequencing and -omics techniques have begun to facilitate a holistic understanding of the transcriptional landscape and its plasticity. We highlight transcription factors, their cofactors, and the pathways that they impact. We also discuss physiological factors that impinge on these responses, including circadian rhythms and sex differences. Finally, we review how dietary modifications modulate hepatic gene expression programs.
    Keywords:  liver; metabolism; transcription
  5. Physiol Behav. 2021 Apr 17. pii: S0031-9384(21)00112-8. [Epub ahead of print] 113420
      Light is the most powerful temporal cue that entrains physiology and behavior through modulation of the suprachiasmatic nucleus (SCN) of the hypothalamus. However, on a daily basis, individuals face a combination of light and several non-photic cues, such as social interaction. In order to investigate whether SCN activity and SCN-driven rhythms are altered by social interaction, adult male C57BLJ/6 mice were maintained in groups of 3-4 animals per cage or 1 animal per cage (socially isolated) under 12:12 h / light:dark (LD) cycles or constant darkness (DD). Analysis of the two anatomical subdivisions (ventral, v and dorsal, d) of the medial SCN revealed an effect of housing conditions on the d-SCN but not on the v-SCN on the number of c-Fos immunoreactive (ir) neurons. As such, 2 h after the light-phase onset d-SCN c-Fos-ir number was lower in single-housed mice under LD. Importantly, under DD there were no effect of housing conditions in the number of c-Fos-ir SCN neurons. Social isolation increased the amplitude and strength of SCN-driven rhythm of body temperature (Tc) entrained to LD and it advanced its onset, uncoupling with spontaneous locomotor activity (SLA) rhythm, without altering endogenous Tc and SLA rhythms expressed under DD. Associated with reduced Tc in the light phase, single-housed mice showed reduced body weight. However, these phenotypes were not accompanied by changes in the number of c-Fos-ir neurons in the preoptic area (POA), which are known to regulate energy metabolism and Tc. Altogether, these results imply that the social interaction masking effect on the d-SCN is added to that of light stimulus, in order to achieve full c-Fos expression in the SCN, which, in turn seems to be required to maintain daily-phase coherence between the photo-entrained rhythms of Tc and SLA. There might be an inter-relationship between masking (social interaction) and entrainment stimulus (light) that impacts the circadian parameters of the photo-entrained Tc rhythm. As such, in the absence of social interactions a more robust Tc rhythm is shown. This inter-relationship seems to occur in the dorsal subdivision of the SCN but not in the POA.
    Keywords:  Circadian clock; Entrainment; Non-photic cues; Social isolation
  6. Appetite. 2021 Apr 02. pii: S0195-6663(21)00147-1. [Epub ahead of print]164 105240
      The interaction between time of day and energy intake, termed chrono-nutrition, has received considerable recent interest. One aspect of chrono-nutrition with potential to benefit long-term cardio-metabolic health is time-restricted feeding (TRF). Current support for TRF primarily derives from animal research, although recent small-scale human studies indicate possible translational benefit. Whether free-living humans, however, can incorporate TRF into their daily lives is poorly understood. This study reports data from participants (n = 608) who completed an online questionnaire to investigate daily routine, likelihood of TRF incorporation within work vs free-days, and key considerations influencing TRF uptake. The majority of participants reported a typical daily feeding window (time between first and last energy intake) of between 10 and 14 h on workdays and free days, 62.7 and 65.5% respectively. Likelihood of adherence to TRF declined with an increase in the proposed restriction of the feeding window by 0.5 to 4-h per day. We then examined data from participants with a typical daily feeding window of 12+ h on workdays (n = 221) and free-days (n = 223) to investigate the likelihood of using TRF, and the most important considerations in making this decision. Of these participants, (n = 132) on workdays and (n = 125) on free days would likely reduce their feeding window by 3-h. Multiple regression analysis revealed that key considerations determining the likelihood of adopting TRF were: cost, time availability, and perceived health benefits (on workdays); wake time, bed time, time availability, motivation to change and perceived health benefits (on free-days). These data provide novel information regarding public attitudes towards TRF and highlight important aspects to be considered when translating controlled laboratory studies to public dietary advice.
    Keywords:  Behaviour; Chronobiology; Circadian; Diet; Fasting; Metabolism
  7. Sci Rep. 2021 Apr 22. 11(1): 8693
      Night shift workers are often associated with circadian misalignment and physical discomfort, which may lead to burnout and decreased work performance. Moreover, the irregular work hours can lead to significant negative health outcomes such as poor eating habits, smoking, and being sedentary more often. This paper uses commercial wearable sensors to explore correlates and differences in the level of physical activity, sleep, and circadian misalignment indicators among day shift nurses and night shift nurses. We identify which self-reported assessments of affect, life satisfaction, and sleep quality, are associated with physiological and behavioral signals captured by wearable sensors. The results using data collected from 113 nurses in a large hospital setting, over a period of 10 weeks, indicate that night shift nurses are more sedentary, and report lower levels of life satisfaction than day-shift nurses. Moreover, night shift nurses report poorer sleep quality, which may be correlated with challenges in their attempts to fall asleep on off-days.
  8. Proc Natl Acad Sci U S A. 2021 Apr 27. pii: e2101818118. [Epub ahead of print]118(17):
      Neuropeptides control rhythmic behaviors, but the timing and location of their release within circuits is unknown. Here, imaging in the brain shows that synaptic neuropeptide release by Drosophila clock neurons is diurnal, peaking at times of day that were not anticipated by prior electrical and Ca2+ data. Furthermore, hours before peak synaptic neuropeptide release, neuropeptide release occurs at the soma, a neuronal compartment that has not been implicated in peptidergic transmission. The timing disparity between release at the soma and terminals results from independent and compartmentalized mechanisms for daily rhythmic release: consistent with conventional electrical activity-triggered synaptic transmission, terminals require Ca2+ influx, while somatic neuropeptide release is triggered by the biochemical signal IP3 Upon disrupting the somatic mechanism, the rhythm of terminal release and locomotor activity period are unaffected, but the number of flies with rhythmic behavior and sleep-wake balance are reduced. These results support the conclusion that somatic neuropeptide release controls specific features of clock neuron-dependent behaviors. Thus, compartment-specific mechanisms within individual clock neurons produce temporally and spatially partitioned neuropeptide release to expand the peptidergic connectome underlying daily rhythmic behaviors.
    Keywords:  circadian; fluorogen-activating protein; neuropeptide release; peptidergic transmission; synapse