Timing of food intake is an emerging aspect of nutrition; however, there is a lack of research accurately assessing food timing in the context of the circadian system. The study aimed to investigate the relation between food timing relative to clock time and endogenous circadian timing with adiposity and further explore sex differences in these associations among 151 young adults aged 18–25 years. Participants wore wrist actigraphy and documented sleep and food schedules in real time for 7 consecutive days. Circadian timing was determined by dim-light melatonin onset (DLMO). The duration between last eating occasion and DLMO (last EO-DLMO) was used to calculate the circadian timing of food intake. Adiposity was assessed using bioelectrical impedance analysis. Of the 151 participants, 133 were included in the statistical analysis finally. The results demonstrated that associations of adiposity with food timing relative to circadian timing rather than clock time among young adults living in real-world settings. Sex-stratified analyses revealed that associations between last EO-DLMO and adiposity were significant in females but not males. For females, each hour increase in last EO-DLMO was associated with higher BMI by 0·51 kg/m2 (P = 0·01), higher percent body fat by 1·05 % (P = 0·007), higher fat mass by 0·99 kg (P = 0·01) and higher visceral fat area by 4·75 cm2 (P = 0·02), whereas non-significant associations were present among males. The findings highlight the importance of considering the timing of food intake relative to endogenous circadian timing instead of only as clock time.

Obesity is a chronic, complex and multi-factorial condition with an increasing prevalence worldwide. Irregular eating schedules might be a contributing factor to these numbers through the dysregulation of the circadian system. Time-restricted eating (TRE), an approach that limits eating windows, has been studied as a strategy to treat obesity, aligning eating occasions with metabolic circadian rhythms. This review aims to provide an overview of the impact of TRE protocols on metabolic, inflammatory, oxidative stress, and circadian rhythm biomarkers in people with overweight or obesity. Most studies report significant weight loss following TRE protocols. While glucose levels decreased in nearly all TRE interventions, only a few studies demonstrated statistically significant differences when compared to the control groups. The findings for CRP and TNF-α were inconsistent, with limited significant differences. Changes in lipid profile changes were variable and generally did not reach statistical significance. Both 4-hour and 6-hour TRE interventions significantly reduced 8-isoprostane levels. Additionally, TRE significantly altered clock gene expression, as well as that of genes associated with metabolic regulation in subcutaneous adipose tissue. While the evidence is still inconsistent, limiting eating to a consistent daily window of 8 to 12 hours can improve insulin sensitivity, reduce blood glucose, cholesterol and triglyceride levels and promote weight loss. These effects are likely attributable to both direct metabolic impacts and indirect benefits from weight loss and improved dietary habits. However, data on circadian, inflammatory, and specific metabolic biomarkers remain scarce and occasionally contradictory, highlighting the need for further research on these interventions.

Chrono-medicine considers circadian biology in disease management, including combined lifestyle and medicine interventions. Exercise and nutritional interventions are well-known for their efficacy in managing type 2 diabetes, and metformin remains a widely used pharmacological agent. However, metformin may reduce exercise capacity and interfere with skeletal muscle adaptations, creating barriers to exercise adherence. Research into optimising the timing of exercise has shown promise, particularly for glycaemic management in people with type 2 diabetes. Aligning exercise timing with circadian rhythms and nutritional intake may maximise benefits. Nutritional timing also plays a crucial role in glycaemic control. Recent research suggests that not only what we eat but when we eat significantly impacts glycaemic control, with strategies like time-restricted feeding (TRF) showing promise in reducing caloric intake, improving glycaemic regulation and enhancing overall metabolic health. These findings suggest that meal timing could be an important adjunct to traditional dietary and exercise approaches in managing diabetes and related metabolic disorders. When taking a holistic view of Diabetes management and the diurnal environment, one must also consider the circadian biology of medicines. Metformin has a circadian profile in plasma, and our recent study suggests that morning exercise combined with pre-breakfast metformin intake reduces glycaemia more effectively than post-breakfast intake. In this review, we aim to explore the integration of circadian biology into type 2 diabetes management by examining the timing of exercise, nutrition and medication. In conclusion, chrono-medicine offers a promising, cost-effective strategy for managing type 2 diabetes. Integrating precision timing of exercise, nutrition and medication into treatment plans requires considering the entire diurnal environment, including lifestyle and occupational factors, to develop comprehensive, evidence-based healthcare strategies.

In the question put forward by Scott et al., implications about the role of immune activation in depressive or other mood disorders were suggested. Low-level inflammation, triggered by the release of inflammatory molecules such as cytokines, has been detected in individuals with major mood disorders. These markers can be present in very low concentrations, posing a significant analytical challenge and complicating their use as reliable biomarkers. In this Perspective, we discuss the potential promise in leveraging nanotechnology and trace-level analysis of biomarkers of immune activation to enhance our molecular understanding of the immune system’s functioning and its association with depressive and other mood disorders. This Perspective critically discusses the analytical challenges of trace biomarker detection, highlighting issues with variability in study methodologies and cohort heterogeneity and emphasising the need for diurnal and longitudinal sampling to study circadian disruption and immune activation. Profiling inflammatory markers in this manner could create individualised molecular fingerprints, revealing disruptions in immune synchronisation with circadian rhythms and detecting abnormalities linked to specific mood disorder subtypes, and particularly ‘circadian depression’. As the profiling of general inflammatory markers may not be sufficient to study any causative relationship between immune activation and major mood disorders, we propose the exploration of novel biomarkers such as extracellular vesicles to support these investigations. The use of nanotechnologies for trace profiling of diurnal variations of inflammatory molecules, in combination with novel biomarkers, offers a promising strategy to develop a molecular understanding of the role of immune activation in depressive and other mood disorders.

Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.

A device for analysing mouse behaviour which is based on recording the movements of the animal in a balance test cage has been developed. The amplitude patterns provoked by the movements of the animal correlate with behavioural patterns. The system not only allows differentiation between five behavioural categories: resting, grooming, eating, locomotion and climbing - but also indicates the location of the animal in its cage. Upon validation, the system has proven to be a reliable and time-saving device for the non-invasive recording of behavioural patterns in the mouse.

Considerable research has pointed towards processing differences as a viable means for understanding the strength and likelihood of a framing effect. In the current study we explored how differences in processing may emerge through diurnal patters in circadian rhythm, which varies across individuals. We predicted that during circadian off-times, participants would exhibit stronger framing effects whereas framing effects would be relatively weaker during on-times. Six-hundred and eighty five individuals took part in the study; the findings supported our hypothesis, revealing a diurnal pattern of risk responding that varies across the 24-hour circadian cycle.

Bipolar disorder (BD) is a potentially chronic mental disorder marked by recurrent depressive and manic episodes, circadian rhythm disruption, and changes in energetic metabolism. “Metabolic jet lag” refers to a state of shift in circadian patterns of energy homeostasis, affecting neuroendocrine, immune, and adipose tissue function, expressed through behavioral changes such as irregularities in sleep and appetite. Risk factors include genetic variation, mitochondrial dysfunction, lifestyle factors, poor gut microbiome health and abnormalities in hunger, satiety, and hedonistic function. Evidence suggests metabolic jet lag is a core component of BD pathophysiology, as individuals with BD frequently exhibit irregular eating rhythms and circadian desynchronization of their energetic metabolism, which is associated with unfavorable clinical outcomes. Although current diagnostic criteria lack any assessment of eating rhythms, technological advancements including mobile phone applications and ecological momentary assessment allow for the reliable tracking of biological rhythms. Overall, methodological refinement of metabolic jet lag assessment will increase knowledge in this field and stimulate the development of interventions targeting metabolic rhythms, such as time-restricted eating.

As an internal time-keeping mechanism, circadian rhythm plays crucial role in maintaining homoeostasis when in response to nutrition change; meanwhile, branched-chain amino acids (BCAA) in skeletal muscle play an important role in preserving energy homoeostasis during fasting. Previous results from our laboratory suggested that fasting can influence peripheral circadian rhythm and BCAA metabolism in fish, but the relationship between circadian rhythm and BCAA metabolism, and whether circadian rhythm regulates BCAA metabolism to maintain physiological homoeostasis during fasting remains unclear. This study shows that the expression of fifteen core clock genes as well as KLF15 and Bcat2 is highly responsive to short-term fasting in fast muscle of Siniperca chuatsi, and the correlation coefficient between Clock and KLF15 expression is enhanced after fasting treatment. Furthermore, we demonstrate that the transcriptional expression of KLF15 is regulated by Clock, and the transcriptional expression of Bcat2 is regulated by KLF15 by using dual-luciferase reporter gene assay and Vivo-morpholinos-mediated gene knockdown technique. Therefore, fasting imposes a dynamic coordination of transcription between the circadian rhythm and BCAA metabolic pathways. The findings highlight the interaction between circadian rhythm and BCAA metabolism and suggest that fasting induces a switch in KLF15 expression through affecting the rhythmic expression of Clock, and then KLF15 promotes the transcription of Bcat2 to enhance the metabolism of BCAA, thus maintaining energy homoeostasis and providing energy for skeletal muscle as well as other tissues.

Meal timing is a key factor in synchronising the circadian clock in peripheral tissues. Circadian disorders are associated with the metabolic syndrome. Previously, we demonstrated that a skipping breakfast regimen (SBR) with a high-fat diet increased body weight gain in rats. In this study, we investigated whether SBR with a normal diet led to abnormal lipid metabolism and muscle metabolism in mice. Male C57BL/6 mice were fed during zeitgeber time (ZT) 12–24 in the control group and ZT 16–24 in the SBR group for 2 weeks. SBR mice showed increased body weight gain and perirenal adipose tissue weight. The plantar muscle weight was decreased in the SBR group compared with that in the control group. Furthermore, SBR delayed the circadian oscillations in clock gene expression in peripheral tissues, such as the liver, adipose tissue and muscle, as well as the oscillations in the expression of lipid metabolism-related genes in the liver and adipose tissue. These results suggest that skipping breakfast over a long period of time is associated with a risk of obesity, the metabolic syndrome and muscle loss, such as sarcopenia.

Renewed interest in studying auxin herbicides (WSSA Group 4) is increasing as a result of the release of genetically engineered crop varieties that are tolerant to preemergence and postemergence applications of specific formulations of dicamba. Auxin-resistant crops were developed in response to the development of weed species resistant to glyphosate and other herbicides. Research was conducted at multiple field locations in Georgia in 2018 and 2019 to examine weed control when postemergence herbicides were applied to dicamba- and glyphosate-resistant cotton at eight different points in time over a 24-h period. Applications were made at 1 h prior to sunrise all the way up to midnight during the same day to examine the effect of herbicide application timing on broadleaf weed control. Glyphosate, dicamba, and glyphosate plus dicamba were applied at each timing. Visual ratings of weed control were scored at 7, 14, 21, and 28 d after treatment (DAT). Weed control was affected by herbicide application timing. Midnight applications resulted in the lowest levels of control. Sicklepod, pitted morningglory, and prickly sida control was 49%, 38%, and 41%, respectively. Greatest control of all three species (up to 99%) occurred from the noon to 1 h prior to sunset application timings. Orthogonal contrasts of timing of application indicated that weed control was improved with day > night and pre-dawn > midnight.