bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2025–08–31
seven papers selected by
Gabriela Da Silva Xavier, University of Birmingham



  1. Proc Biol Sci. 2025 Aug;292(2053): 20251170
      Light pollution is a major anthropogenic environmental change and a significant threat to ecosystems. Among other detrimental effects on physiology, artificial light at night (ALAN) disrupts circadian rhythms in a wide range of species. However, the underlying neuronal and genetic mechanisms remain poorly understood. Here, we show in Drosophila that the loss of the circadian clock gene period exacerbates the ALAN-induced shift towards nocturnal behaviour, with a more pronounced effect on males. In contrast, the loss of cycle has no such effect on males or females; cyc null mutants are nocturnal under standard light‒dark cycles, and their activity and sleep profiles are minimally or not affected by ALAN exposure. CRISPR-Cas9 knockout of period in most clock neurons resembles the null mutant phenotype. Our results show that mutations in components of the positive and negative limbs of the circadian clock result in distinct responses to nocturnal light and highlight the role of genetic factors in modulating behavioural plasticity in response to environmental perturbations.
    Keywords:  Drosophila; artificial light at night; behavioural genetics; circadian rhythms; clock genes; sex differences
    DOI:  https://doi.org/10.1098/rspb.2025.1170
  2. Wellcome Open Res. 2025 ;10 172
       Background: Accurately measuring activity and feeding is important in laboratory animal research, whether for welfare-monitoring or experimental recording. Quantification commonly involves manual pellet-weighing; however, this can physically disturb animals and cannot continuously assess both the amount and pattern of feeding over time. Improved means of food-intake measurement have been developed but can be costly and incompatible with many cage configurations.
    Methods: We developed the SnackerTracker-a novel home-cage monitoring system which continuously records food-intake, food-seeking activity, and ambient light conditions in laboratory mice. After benchtop validations, we tested this device by recording from C57BL/6J control mice under 12:12h light:dark (LD) and constant darkness (DD) to measure circadian rhythms in feeding behaviour. We then recorded from mice having disturbed circadian rhythms (cryptochrome 1 and 2 double-knockouts, Cry1 -/-,Cry2 -/- ), where irregular activity and feeding patterns were expected. Animals were individually housed with SnackerTrackers in Digital Ventilated Cages ® (DVC, Tecniplast) to measure home cage activity. After habituation, 48-hour SnackerTracker and DVC recordings were collected and compared.
    Results: The SnackerTracker accurately measured food-masses throughout benchtop and in vivo validation tests. Time-course SnackerTracker feeding traces correlated well with DVC activity recordings, indicating that feeding reflects general cage locomotion in control and cryptochrome-deficient animals. In LD, SnackerTracker data showed expected feeding/fasting cycles in control and cryptochrome-deficient animals yet reduced dark-phase feeding in cryptochrome-deficient mice. In DD, increased feeding during the subjective nighttime was maintained in control animals but abolished in cryptochrome-deficient mice. Surprisingly, cryptochrome-deficient animals exhibited ultradian feeding rhythms.
    Conclusions: We validate the performance and value of monitoring home cage feeding using the SnackerTracker. Here we show that cryptochrome-deficient animals have decreased food-intake in LD, diurnal arrhythmicity in DD, and ultradian rhythms in feeding behaviour. The SnackerTracker provides a cost-effective, open-source, and user-friendly method of animal food intake and activity measurement.
    Keywords:  Home-cage monitoring; activity tracking; animal behaviour; animal welfare; biological rhythms; circadian; cryptochrome; food measurement
    DOI:  https://doi.org/10.12688/wellcomeopenres.23850.2
  3. Cell Metab. 2025 Aug 19. pii: S1550-4131(25)00356-0. [Epub ahead of print]
      The circadian clock controls 24-h rhythmic processes. However, how genetic variations outside clock genes impact peripheral diurnal rhythms remains largely unknown. Here, we find that genetic variation contributes to different diurnal patterns of hepatic gene expression in both humans and mice. Nutritional challenges alter the rhythmicity of gene expression in mouse liver in a strain-specific manner. Remarkably, genetics and nutrition interdependently control more than 80% of rhythmic gene and enhancer-promoter interactions (E-PIs), with a noncanonical clock regulator, estrogen-related receptor gamma (ESRRγ), emerging as a top transcription factor during motif mining. Knockout of Esrrγ abolishes strain-specific metabolic processes in response to diet in mice, while single-nucleotide polymorphisms (SNPs) associated with rhythmic gene expression are enriched in E-PIs in steatotic human livers and correlate with lipid metabolism traits. These findings reveal a previously underappreciated temporal aspect of genetics-environment interaction in regulating lipid metabolic traits, with implications for individual variations in obesity-associated disease susceptibility and personalized chronotherapy.
    Keywords:  3D enhancer-promoter interaction; diurnal rhythm; genetic variation; human metabolic traits; metabolic disorders
    DOI:  https://doi.org/10.1016/j.cmet.2025.07.010
  4. Reprod Biol. 2025 Aug 19. pii: S1642-431X(25)00063-4. [Epub ahead of print]25(4): 101056
      The circadian clock is constructed by a transcription-translation feedback loop system of clock genes and regulates various reproductive physiological functions. Understanding the rhythms of clock gene expression is important for understanding biological rhythms. However, the in vivo clock gene expression rhythm in Japanese Black breeding cows has not yet been clarified. Herein, we investigated the circadian expression rhythm of clock genes in hair follicle cells in the hair roots of Japanese Black breeding cows. We found that the clock genes of Japanese Black breeding cows exhibit an expression rhythm with a period of approximately 24 h under natural light, similar to the pattern observed in mice and humans, and that this expression rhythm disappears under constant light conditions. Furthermore, since the expression levels of clock genes are significantly reduced in pregnant cows exposed to constant light conditions, we analysed the diurnal variation in the plasma concentration of progesterone, which plays an important role in maintaining pregnancy. We found that the progesterone secretion rhythm observed under natural light in pregnant cows also disappeared under constant light conditions. These results indicate that in Japanese Black breeding cows, clock genes exhibit a diurnal expression rhythm in response to light; this rhythm disappears under constant light conditions. These clock genes play important roles in the diurnal variation in hormone secretion by interacting with progesterone in the blood.
    Keywords:  Circadian clock; Clock gene; Hair follicle cells; Japanese Black cow; Progesterone
    DOI:  https://doi.org/10.1016/j.repbio.2025.101056
  5. Diabetes Metab Syndr. 2025 Aug 20. pii: S1871-4021(25)00101-8. [Epub ahead of print]19(7): 103284
       BACKGROUND: Misalignment of the endogenous circadian system may contribute to the risk of type 2 diabetes. This systematic review and meta-analysis examined the association between clock gene polymorphisms and glycemic parameters and type 2 diabetes.
    METHODS: Embase, Medline, and Web of Science databases were searched from inception to August 20, 2024. Empirical studies examining the association between core clock gene polymorphisms and type 2 diabetes and glycemic parameters, and studies examining non-core clock genes with information on environmental factors were included. A multi-level meta-analytical approach was used, and a weighted odds ratio was reported (PROSPERO, CRD42022337706).
    RESULTS: In total, 37 studies comprising 535,063 participants were included. CRY2 was associated with higher fasting blood glucose (OR: 1.07, 95 % CI: 1.03-1.11) and impaired glucose tolerance (OR: 1.02, CI: 1.00-1.04). Polymorphisms in MTNR1B were associated with a greater risk of type 2 diabetes. CLOCK was associated with lower risk of type 2 diabetes (OR: 0.94, CI: 0.89-1.00), and PER3 was associated with lower fasting insulin (OR: 0.94, CI: 0.91-0.97) and lower risk of insulin resistance (OR: 0.92, CI: 0.88-0.95). These associations reflect pooled variant-level effects within genes, and the effects of certain variants were modified by diet, alcohol consumption, physical activity, sleep, and length of daylight.
    CONCLUSIONS: Specific polymorphisms in circadian genes, including CRY2, MTNR1B, CLOCK, and PER3, were associated with glycemic parameters and type 2 diabetes risk. These associations may be influenced by lifestyle and environmental factors, and interventions targeting circadian alignment could potentially modify diabetes risk, although further research is needed.
    Keywords:  Chronotype; Circadian rhythm; Clock genes; Type 2 diabetes
    DOI:  https://doi.org/10.1016/j.dsx.2025.103284
  6. Sci Rep. 2025 Aug 25. 15(1): 31178
      24-h cycles regulate activity and feeding behavior, and obesity and metabolic dysfunction may disrupt such rhythms. Here, using a fixed 24-h light-dark cycle, we investigate sex-specific diurnal physical activity patterns in obese and normal weight mice. We observe that feeding behavior aligns with a mid-dark cycle activity peak. Using passive home cage monitoring and operant feeding tasks, we demonstrate that male and female mice exhibit distinct temporal activity profiles, particularly during the late dark cycle. Diet-induced obesity selectively suppressed mid-dark cycle activity, a temporal window linked to peak food-seeking behavior. These findings highlight temporal disruptions to physical activity in a rodent model of diet-induced obesity and offer insights into potential interactions between feeding behavior and 24 physical activity patterns.
    Keywords:  Feeding behavior; Obesity; Physical activity; Sex differences
    DOI:  https://doi.org/10.1038/s41598-025-16084-4
  7. Plants (Basel). 2025 Aug 08. pii: 2464. [Epub ahead of print]14(16):
      Plants align their physiology with daily environmental cycles through the circadian clock, which integrates light and metabolic signals to optimize growth and stress responses. While light entrainment has been extensively studied, emerging evidence highlights the central role of metabolism-particularly from chloroplasts and mitochondria-in tuning circadian rhythms. In this review, we explore the bidirectional relationship between organelle metabolism and the circadian clock, focusing on how metabolic signals such as sugars, ROS, and organic acids function as entrainment cues. We discuss how the clock regulates organelle function at multiple levels, including transcriptional, translational, and post-translational mechanisms, and how organelle-derived signals feedback to modulate core clock components through retrograde pathways. Special attention is given to the integration of chloroplast and mitochondrial signals, emphasizing their synergistic roles in maintaining cellular homeostasis. Drawing on the "three-body problem" analogy, we illustrate the dynamic and reciprocal interactions among light, clock, and metabolism. This perspective underscores the need to reframe the circadian system, not merely as light-driven but also as a central integrator of energy status and environmental cues. Understanding this integrated network is essential to improve plant performance and resilience under fluctuating environmental conditions.
    Keywords:  chloroplast–mitochondria crosstalk; circadian clock; light signaling; metabolic entrainment; plant energy metabolism; retrograde signaling
    DOI:  https://doi.org/10.3390/plants14162464