bims-ciryme 2025-05-04 papers

EMBO Rep. 2025 Apr 30.

Genetic disruption of the circadian gene Bmal1 in the intestinal epithelium reduces colonic inflammation.

Shan Hua, Ze Zhang, Zhe Zhang, Liansheng Liu, Shicheng Yu, Yanhui Xiao, Yuan Liu, Siting Wei, Ying Xu, Ye-Guang Chen.

Disruption of the circadian clock is associated with the development of inflammatory bowel disease (IBD), but the underlying mechanisms remain unclear. Here, we observe that mice in the early active phase (Zeitgeber time 12, ZT12) of the circadian clock are more tolerant to dextran sodium sulfate (DSS)-induced colitis, compared to those in the early resting phase (ZT0). The expression of the circadian gene Bmal1 peaks in the early resting phase and declines in the early active phase. Bmal1 knockout in the intestinal epithelium reduces DSS-induced inflammatory symptoms. Mechanistically, BMAL1 promotes apoptosis by binding to apoptosis-related genes, including Bax, p53, and Bak1, and promotes their expression. Intriguingly, we observe circadian apoptotic rhythms in the homeostatic intestinal epithelium, while Bmal1 deletion reduces cell apoptosis. Consistently, reducing Bmal1 expression by the REV-ERBα agonist SR9009 has the best therapeutic efficacy against DSS-induced colitis at ZT0. Collectively, our data demonstrate that the Bmal1-centered circadian clock is involved in intestinal injury repair.

Keywords: Bmal1; Circadian Rhythm; Colitis; Intestinal Homeostasis

DOI: https://doi.org/10.1038/s44319-025-00464-y

Sci Rep. 2025 Apr 28. 15(1): 14884

When lowering temperature, the in vivo circadian clock in cyanobacteria follows and surpasses the in vitro protein clock trough the Hopf bifurcation.

Irina Mihalcescu, Hotaka Kaji, Hina Maruyama, Jerôme Giraud, Mathilde Van Melle-Gateau, Bahram Houchmandzadeh, Hiroshi Ito.

The in vivo circadian clock in single cyanobacteria is studied here by time-lapse fluorescence microscopy when the temperature is lowered below 25°C. We first disentangle the circadian clock behavior from the bacterial cold shock response by identifying a sequence of "death steps" based on cellular indicators. By analyzing only "alive" traces, we show that the dynamic response of individual oscillatory traces to a step-down temperature signal is described by a simple Stuart-Landau oscillator model. The same dynamical analysis applied to in vitro data (KaiC phosphorylation level following a temperature step-down) allows for extracting and comparing both clock's responses to a temperature step down. It appears, therefore, that both oscillators go through a similar supercritical Hopf bifurcation. Finally, to quantitatively describe the temperature dependence of the resulting in vivo and in vitro Stuart-Landau parameters [Formula: see text] and [Formula: see text], we propose two simplified analytical models: temperature-dependent positive feedback or time-delayed negative feedback that is temperature compensated. Our results provide strong constraints for future models by revealing a specific time scale for transitory regimes in the cyanobacterial circadian system and its temperature dependence.

DOI: https://doi.org/10.1038/s41598-025-97412-6

Sci Rep. 2025 Apr 29. 15(1): 14952

Characterization of the daily and circadian valve behavior of the European flat oyster Ostrea edulis.

Alexandre Le Moal, Damien Tran, Laura Payton, Bernadette Pogoda, Bettina Meyer.

Marine organisms exhibit a multitude of biological rhythms synchronized with the interactions of the sun-, earth-, and moon cycles. However, the biological rhythms in bivalves remain poorly studied. This study focuses on the native European flat oyster (Ostrea edulis), an endangered species of coastal ecosystems and a key organism in restoring of biogenic reef habitats. We aim to determine whether a molecular endogenous circadian rhythm exists in O. edulis and to characterize its daily expression. To address these questions, the oysters' valve behavior, as an output of the circadian clock expression, was recorded under different light conditions and free-running regimes using non-invasive valvometry. This work demonstrates the existence of a circadian clock mechanism that generates a labile behavioral circadian oscillation under free-running conditions. In light: dark conditions, a diel rhythm appears nocturnal, synchronizable to a shift of light phase, and remains unmodified whether the oysters are fed or not. This rhythm anticipates light: dark changes, indicating its endogenous origin. Finally, when exposed to artificial light at night the daily behavior is disrupted. This study characterizes the circadian behavioral rhythm of O. edulis's as plastic and labile. This plasticity would be advantageous in terms of ecological adaptability but increases sensitivity to anthropogenic pressures such as light pollution.

Keywords: Ostrea edulis ; Circadian rhythm; Daily rhythm; Free-running; Oysters; Valve behavior

DOI: https://doi.org/10.1038/s41598-025-98746-x

Nutr Res. 2025 Mar 27. pii: S0271-5317(25)00045-4. [Epub ahead of print]138 33-44

Comparing the effectiveness of calorie restriction with and without time-restricted eating on the circadian regulation of metabolism: rationale and protocol of a three-arm randomised controlled trial in adults at risk of type 2 diabetes.

You Jin Chang, Laurent Turner, Xiao Tong Teong, Lijun Zhao, Athena Variji, Gary A Wittert, Sophia Thompkins, Andrew D Vincent, Linda Grosser, Morag J Young, Stephen Blake, Satchidananda Panda, Emily N C Manoogian, Siobhan Banks, Leonie K Heilbronn, Amy T Hutchison.

Time-restricted eating (TRE) may extend the cardiometabolic health benefits of calorie restriction (CR). However, few studies have compared its effect on the circadian regulation of glucose metabolism and the optimal time of day to initiate TRE is also unclear. This study aims to compare the effectiveness of CR with and without TRE on glucose tolerance in response to 3 identical meals consumed over the day. A parallel, single-blinded, 3-arm randomised controlled trial will be conducted in 114 adults, aged 35 to 75 years with a BMI ≥25.1 but <45.0 kg/m2, elevated waist circumference and fasting blood glucose (≥5.6 mmol/L), and who score ≥12 on the Australian Type 2 Diabetes Risk Assessment tool. Participants will be stratified by sex and fasting blood glucose (≤6.0 mmol/L; >6.0 mmol/L) and then randomised (1:1:1) to CR (unrestricted meal timing), eCR (0800 to 1600) or dCR (1200-2000) for 8 weeks. The primary outcome is the change in the natural logarithm of the mean over 3 identical meals of the postprandial glucose area under the curve (AUC). The analysis will be performed using a covariate adjusted linear regression of the differences in postprandial glucose log AUC at 8 weeks from baseline. This randomised clinical trial will be the first to delineate the benefits of CR alone or in combination with time restricted eating on postprandial glucose metabolism over the day in adults at increased risk of type 2 diabetes.

Keywords: Calorie restriction; Cardiometabolic health; Glucose control; Obesity; Time-restricted eating

DOI: https://doi.org/10.1016/j.nutres.2025.03.009