bims-ciryme 2025-12-21 papers

Cell Metab. 2025 Dec 18. pii: S1550-4131(25)00490-5. [Epub ahead of print]

Natural daylight during office hours improves glucose control and whole-body substrate metabolism.

Because 80%-90% of our time is spent indoors and daylight is the main synchronizer of the central biological clock, the chronic lack of daylight is increasingly considered as a risk factor for metabolic diseases, such as type 2 diabetes. In a randomized crossover design (NCT05263232), 13 individuals with type 2 diabetes were exposed to natural daylight facilitated through windows vs. constant artificial lighting during office hours for 4.5 consecutive days. Continuous glucose monitoring revealed that participants spent more time in the normal glucose range, and whole-body substrate metabolism shifted toward a greater reliance on fat oxidation during daylight. Primary myotubes cultured from skeletal muscle biopsies displayed a phase advance after daylight exposure. Multi-omic analyses revealed daylight-induced differences in serum metabolites, lipids, and monocyte transcripts. Our findings suggest that natural daylight exposure has a positive metabolic impact on individuals with type 2 diabetes and could support the treatment of metabolic diseases.

Keywords: artificial light; circadian clocks; daylight; glucose control; melatonin; multi-omics; skeletal muscle; type 2 diabetes

DOI: https://doi.org/10.1016/j.cmet.2025.11.006

Commun Biol. 2025 Dec 17.

Immediate nuclear accumulation of BMAL1 to regulate cellular circadian clock synchronization.

Teruya Tamaru, Genki Kawamura, Hikari Yoshitane, Satoshi Koinuma, Yoshitaka Fukada, Atsuhiko Naito, Takeaki Ozawa, Ken Takamatsu.

Cell-autonomous circadian clocks coordinate daily physiological timing, allowing them to synchronize with the environment. However, the initial signaling events shared by diverse synchronizing cues remain elusive. Here, we show that changes in the clock protein localization serve as a common synchronizing event by investigating the relationship between BMAL1 and CLOCK localization patterns and clock synchronization in NIH-3T3 fibroblasts. We demonstrate synchronized nuclear BMAL1 accumulation as an immediate synchronization response (ISR), as well as CLOCK accumulation following various clock-resetting treatments. BMAL1-Ser90 phosphorylation by CK2, which is reported to promote nuclear BMAL1 accumulation, is also immediately elevated. Importantly, pharmacological CK2 inhibition partially suppresses the acute Per2 increase and clock reset. Furthermore, computational simulation supports that an increase in the BMAL1 phosphorylation levels and its subsequent nuclear localization could reset the clock. In summary, our findings suggest that BMAL1-ISR is a key event that acts as an integrative switching signal to link molecular clock oscillation and diverse synchronization cues.

DOI: https://doi.org/10.1038/s42003-025-09373-1

Neuroscience. 2025 Dec 12. pii: S0306-4522(25)01175-3. [Epub ahead of print]

Characterization of the expression and function of schizophrenia risk gene Dtnbp1 in the suprachiasmatic nucleus.

Genavieve Elizabeth Maloney, Marie-Ève Cloutier, Micah Joseph Provost, Lalit K Srivastava, Nicolas Cermakian.

Schizophrenia (SZ) is a debilitating neurodevelopmental disorder with environmental and genetic origins. Circadian rhythm disruption is observed in a large proportion of patients with SZ. We previously found that Sandy (Sdy) mice, which carry a mutation in the SZ-associated gene dystrobrevin binding protein 1 (Dtnbp1, also called Dysbindin-1), show altered rhythms of locomotor activity. To address the possible mechanisms underlying the circadian phenotype of these mice, we set out to address the expression and function of Dtnbp1 in the suprachiasmatic nucleus (SCN), the location of the central circadian clock in mammals. Immunohistochemistry revealed that DTNBP1 protein was expressed throughout the SCN, with stronger expression in the dorsal part. DTNBP1 immunoreactive signal colocalized with neurons expressing either arginine vasopressin peptide (AVP) or vasoactive intestinal peptide (VIP). Fluorescent in situ hybridization showed a time-dependent variation of expression of Dtnbp1 transcript, and confirmed its location in cell bodies of AVP- and VIP-expressing cells. Since DTNBP1 is known to be implicated in synaptic transmission, we studied the effect of Dtnbp1 gene mutation on SCN neuropeptide expression and neuroanatomy in Sdy mice. There was no significant effect of the Dtnbp1 mutation on AVP and VIP expression in the SCN. We then used transmission electron microscopy to study synaptic morphology and secretory vesicles. There was no effect of the Dtnbp1 mutation on these neuroanatomical features. Our data show that Dtnbp1 is expressed with a daily rhythm across the SCN, but that a loss-of-function mutation did not impair AVP or VIP neuropeptide expression nor general synaptic architecture.

Keywords: Arginine vasopressin peptide; Circadian disruption; Dtnbp1; Schizophrenia; Suprachiasmatic nucleus; Vasoactive intestinal peptide

DOI: https://doi.org/10.1016/j.neuroscience.2025.12.029

Nat Commun. 2025 Dec 13.

Circadian rhythm profiles derived from accelerometer measures of the sleep-wake cycle in two cohort studies.

Sam Vidil, Ian Meneghel Danilevicz, Aline Dugravot, Aurore Fayosse, Benjamin Landré, Vincent van Hees, Mathilde Chen, Archana Singh-Manoux, Séverine Sabia.

Accelerometers allow objective measures of dimensions (rest-activity rhythm (RAR), daytime activity, sleep, and chronotype) of the bio-behavioural manifestation of circadian rhythm (CR) using multiple metrics in large-scale studies. These dimensions are rarely examined together due to methodological challenges of using correlated data. To address this challenge, we propose a two-step approach consisting of data reduction of CR metrics using principal component analyses, followed by k-means clustering to identify groups of individuals with a similar profile using data from the Whitehall II (N = 3,991, mean age=69.4years) and UK Biobank (N = 54,995, mean age=67.5years) cohort studies. Our analyses identified nine CR clusters: two presented extreme (most robust/poorest) RAR and (highest/lowest) daytime activity, two robust RAR with opposite sleep profiles (longer and efficient/shorter and fragmented), one high-intensity physical activity, and four poor RAR (one characterised by late chronotype, two by low activity but opposite sleep profiles, and one by restless (agitated) sleep). The participants in these nine clusters differed on sociodemographic, behavioural and health-related factors. Findings were similar in these two independent cohort studies, highlighting the validity of our approach. Most previous studies have used only the RAR dimension of circadian rhythm, and here we show that this might be an oversimplification as demonstrated by nine clusters characterised by combinations of RAR, daytime activity, sleep, and chronotype. Our innovative approach demonstrates feasibility of using all dimensions to study the impact of circadian rhythm dysregulation on health.

DOI: https://doi.org/10.1038/s41467-025-66407-2