bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2022‒03‒20
five papers selected by
Gabriela Da Silva Xavier
University of Birmingham

  1. PLoS Biol. 2022 Mar;20(3): e3001571
      Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice.
  2. Front Physiol. 2022 ;13 830107
      Circadian clocks are an intrinsic element of life that orchestrate appropriately timed daily physiological and behavioural rhythms entrained to the solar cycle, thereby conferring increased fitness. However, it is thought that the first archaic 'proto-clocks' evolved in ancient cyanobacteria in a marine environment, where the dominant time cues (zeitgebers) probably would have been lunar-driven and included tidal cycles. To date, non-circadian 'marine clocks' have been described with circatidal (~12.4 h), circasemilunar (~14.8 days), and circalunar (~29.5 days) periodicity, mostly studied in accessible but temporally complex intertidal habitats. In contrast to the well-described circadian clock, their molecular machinery is poorly understood, and fundamental mechanisms remain unclear. We propose that a multi-species approach is the most apposite strategy to resolve the divergence that arose from non-circadian clockwork forged in an evolutionary environment with multiple zeitgebers. We review circatidal clock models with a focus on intertidal organisms, for which robust behavioural, physiological, or genetic underpinnings have been explicated, and discuss their relative experimental merits. Developing a comprehensive mechanistic understanding of circatidal clocks should be a priority because it will ultimately contribute to a more holistic understanding of the origins and evolution of chronobiology itself.
    Keywords:  chronobiology; circadian; circatidal; evolution; intertidal; lunar; marine; mechanistic understanding
  3. Front Endocrinol (Lausanne). 2022 ;13 841838
      Background: Randomized controlled trials of time restricted eating (TRE) in adults have demonstrated improvements in glucose variability as captured by continuous glucose monitors (CGM). However, little is known about the feasibility of CGM use in TRE interventions in adolescents, or the expected changes in glycemic profiles in response to changes in meal-timing. As part of a pilot trial of TRE in adolescents with obesity, this study aimed to 1) assess the feasibility of CGM use, 2) describe baseline glycemic profiles in adolescents with obesity, without diabetes, and 3) compare the difference between glycemic profiles in groups practicing TRE versus control.Methods: This study leverages data from a 12-week pilot trial ( Identifier: NCT03954223) of late TRE in adolescents with obesity compared to a prolonged eating window. Feasibility of CGM use was assessed by monitoring 1) the percent wear time of the CGM and 2) responses to satisfaction questionnaires. A computation of summary measures of all glycemic data prior to randomization was done using EasyGV and R. Repeat measures analysis was conducted to assess the change in glycemic variability over time between groups. Review of CGM tracings during periods of 24-hour dietary recall was utilized to describe glycemic excursions.
    Results: Fifty participants were enrolled in the study and 43 had CGM and dietary recall data available (16.4 + 1.3 years, 64% female, 64% Hispanic, 74% public insurance). There was high adherence to daily CGM wear (96.4%) without negative impacts on daily functioning. There was no significant change in the glycemic variability as measured by standard deviation, mean amplitude glycemic excursion, and glucose area under the curve over the study period between groups.
    Conclusions: CGM use appears to be a feasible and acceptable tool to monitor glycemic profiles in adolescents with obesity and may be a helpful strategy to confirm TRE dosage by capturing glycemic excursions compared to self-reported meal timing. There was no effect of TRE on glucose profiles in this study. Further research is needed to investigate how TRE impacts glycemic variability in this age group and to explore if timing of eating window effects these findings.
    Keywords:  adherence - compliance - persistence; adolescent; continuous glucose monitor (CGM); glycemic excursion; glycemic profile; obesity; time restricted eating
  4. Sleep. 2022 Mar 15. pii: zsac065. [Epub ahead of print]
      STUDY OBJECTIVES: While light therapy has proven effective in re-entraining circadian rhythms, the potential of such an intervention has not been evaluated systematically in post-comatose patients with disorders of consciousness (DOC), who often have strongly altered circadian rhythms.METHODS: We recorded skin temperature over 7-8 days in patients with DOC in each of two conditions: habitual light (HL), and dynamic daylight (DDL) condition. While patients were in a room with usual clinic lighting in the HL condition, they were in an otherwise comparable room with biodynamic lighting (i.e. higher illuminance and dynamic changes in spectral characteristics during the day) in the DDL condition. To detect rhythmicity in the patients' temperature data, we computed Lomb-Scargle periodograms and analysed normalized power, and peak period. Furthermore, we computed interdaily stability and intradaily variability, which provide information about rhythm entrainment and fragmentation.
    RESULTS: We analysed data from 17 patients with DOC (i.e. unresponsive wakefulness syndrome [n=15] and minimally conscious state [n=2]). The period length of the patients' temperature rhythms was closer to 24h in the DDL as compared to the HL condition (median deviation from 24h: HL=3.62h, DDL=0.52h). Specifically, in 11/17 (65%) patients the period length was closer to 24h in the DDL condition. Furthermore, the patients' rhythm was more pronounced, more stable, and less variable in the DDL condition.
    CONCLUSIONS: Our results indicate that DDL stimulation entrains and stabilizes circadian rhythms. This highlights the importance of adequate room lighting as an adjunct therapeutic approach for improving circadian rhythms in severely brain-injured patients.
    Keywords:  Brain injury; Circadian rhythms; Daylight; Disorders of consciousness; Light Therapy; Skin temperature
  5. Mol Psychiatry. 2022 Mar 17.
      Although circadian and sleep disorders are frequently associated with autism spectrum disorders (ASD), it remains elusive whether clock gene disruption can lead to autistic-like phenotypes in animals. The essential clock gene Bmal1 has been associated with human sociability and its missense mutations are identified in ASD. Here we report that global Bmal1 deletion led to significant social impairments, excessive stereotyped and repetitive behaviors, as well as motor learning disabilities in mice, all of which resemble core behavioral deficits in ASD. Furthermore, aberrant cell density and immature morphology of dendritic spines were identified in the cerebellar Purkinje cells (PCs) of Bmal1 knockout (KO) mice. Electrophysiological recordings uncovered enhanced excitatory and inhibitory synaptic transmission and reduced firing rates in the PCs of Bmal1 KO mice. Differential expression of ASD- and ataxia-associated genes (Ntng2, Mfrp, Nr4a2, Thbs1, Atxn1, and Atxn3) and dysregulated pathways of translational control, including hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling, were identified in the cerebellum of Bmal1 KO mice. Interestingly, the antidiabetic drug metformin reversed mTORC1 hyperactivation and alleviated major behavioral and PC deficits in Bmal1 KO mice. Importantly, conditional Bmal1 deletion only in cerebellar PCs was sufficient to recapitulate autistic-like behavioral and cellular changes akin to those identified in Bmal1 KO mice. Together, these results unveil a previously unidentified role for Bmal1 disruption in cerebellar dysfunction and autistic-like behaviors. Our findings provide experimental evidence supporting a putative role for dysregulation of circadian clock gene expression in the pathogenesis of ASD.