Journal of Biological Rhythms最新文献

Rhythmicity is a central feature of behavioral and physiological processes, including sleep, immune responses, and metabolism. Research on brain control of these processes has largely focused on neurons, with less known about the role of clock genes in glial cells. In this study, we addressed the function of glial clocks by targeting the expression of key clock genes in glia of Drosophila melanogaster. Loss of the period (per) gene in glia increases sleep following aseptic injury and loss of either per or timeless (tim) significantly reduces locomotor activity in light:dark cycles and in constant dark, but other than this, the major effect of clock gene loss in glia is on metabolic function. We demonstrate that disruption of either tim or per in glia affects glycogen stores and reduces metabolic rate. Disruption of either tim or per in glia also affects rhythms of feeding and overall food consumption. Notably, these effects of clock disruption are mediated by distinct glial subtypes, especially cortex glia. We propose that the major role of glial clocks is in the control of energy homeostasis and metabolic rhythms, which likely also accounts for effects on locomotor activity. These findings link metabolism and behavior via circadian regulation in glia.

Newly emerging evidence underscores the crucial role of the gut microbiota in regulating various aspects of mammalian physiology and behavior, including circadian rhythms. These rhythms, fundamental to behavioral and physiological processes, are orchestrated by a circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Extra-SCN oscillators have been identified in brain regions beyond the SCN and in peripheral tissues temporizing wide physiological functions. Under a 12 h light: 12 h dark cycle (12:12 LD), restriction of food access to hours of light in nocturnal animals in a time-restricted feeding (TRF) protocol increases locomotor activity preceding the scheduled daily meal, so-called food anticipatory activity (FAA). This circadian behavior is independent from the SCN and controlled by a food-entrainable oscillator (FEO) dependent on reward-related signals. It is known that signals from the gut microbiota regulate behaviors such as motivation oriented by food reward. Thus, we hypothesized a physiological link between gut microbiota and FEO activity by studying the circadian FAA behavior under TRF and assessing food-oriented motivational behavior. For that aim, C57BL/6J mice treated with antibiotics for generating gut microbiota dysbiosis were subjected to a 3 h TRF protocol at zeitgeber time (ZT) 4-7. Mice treated with antibiotics exhibited greater FAA, lower time for its consolidation, and greater motivation levels for food reward. Moreover, tyrosine hydroxylase (TH) levels were increased in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of antibiotic-treated mice. Finally, changes in the gut microbiota composition-including bacterial diversity and the abundance of certain genera-were observed. These results suggest that gut microbiota has a regulatory role in the circadian motivational output for food reward controlled by the FEO. Understanding this role is important for potential chronotherapeutics targeting gut microbiota in reward-related alterations such as addictions and eating disorders.

Time-restricted feeding (TRF), a dietary intervention that consolidates food intake to specific hours of the day, ameliorates key metabolic risk factors for metabolic-associated steatohepatitis (MASH), including adiposity, insulin resistance, and liver steatosis. However, whether TRF can directly mitigate steatohepatitis or fibrosis remains uncertain. Moreover, whether the protective effects of TRF against MASH-related complications, such as inflammation and fibrosis, depend exclusively on improvements in insulin sensitivity or involve additional mechanisms remains unknown. Here, we examine the impact of 8-hour TRF on the development of fibrosis and steatohepatitis using a streptozotocin/high-fat diet (STAM/HFD) model, which recapitulates key MASH characteristics, including steatohepatitis and fibrosis, in an insulin-deficient context. TRF does not prevent the development of MASH in STAM/HFD male mice where insulin signaling is impaired. Unlike diet-induced obesity models, which exhibit greatly perturbed feeding and circadian behaviors under HFD conditions, STAM/HFD mice did not develop obesity and maintained regular or less-pronounced disruptions to circadian behaviors. This may explain why TRF failed to produce beneficial effects in this model. These findings indicate that intact insulin signaling is likely essential for TRF to effectively protect against MASH.

Chronobiology is one of the broadest disciplines in science - we can study and apply this system from molecules to shiftwork, from individuals to populations, from physiology to psychology, from mechanisms to medicine. Since I have an aversion against thinking in boxes, chronobiology was the only discipline I could faithfully live in for the past 55 years, giving me the privilege to witness its epitaxy from its pioneers to circadian medicine. I have tackled chronobiological questions with many different methods, but by far my favorite tool to understand are concepts.

We present a comprehensive analysis of the historical fluctuations and rephasing of seasonal birth rates in the United Kingdom from 1955 to 2015. We analyzed monthly live-birth records for England and Wales together with national photoperiod and surface-temperature series to track the annual rhythm of human reproduction. Fast Fourier transforms confirmed a robust 12-month component across the entire record, but breakpoint tests located a sharp phase shift in 1974-1976. Before this transition, peak conceptions clustered tightly around the summer solstice and yielded a stable March birth maximum. After 1976, the rhythm decoupled: the spring peak in births collapsed, a secondary autumn peak emerged, and inter-annual phase variability more than doubled. Cross-correlation analyses showed that, up to 1974, photoperiod led birth counts by ≈11 months whereas temperature played only a minor role. Post 1976, photoperiod correlations disappeared and a weaker, inverse link with temperature persisted. Sliding-window statistics indicate that variability has narrowed again since the mid-1990s, hinting at partial re-stabilization of the seasonal pattern, now centered in late autumn conceptions. These results demonstrate that the mid-1970s marked a singular disruption of the United Kingdom's reproductive calendar, coincident with the nationwide roll-out of freely available hormonal contraception and other social shifts. The findings urge caution when pooling pre- and post-1974 cohorts in genetic or epidemiological studies-such as those using UK Biobank-to explore season-of-birth effects. More broadly, they highlight the plasticity of human annual timing and the need to disentangle biological from socio-environmental drivers of reproduction.

In adult samples, tightly-controlled laboratory studies indicate the presence of circadian rhythms in positive (and negative) affect. Naturalistic studies also suggest the presence of diurnal positive affect rhythms in adults, the characteristics (acrophase, mesor, and amplitude) of which vary by self-report circadian preference-greater evening preference is associated with later acrophase, lower mesor, and lower amplitude in positive affect. We examined the extent to which diurnal affect rhythms are associated with 4 different measures of circadian timing, including dim light melatonin onset, in a sample of high-school adolescents who reported at least one drink of alcohol in their lifetime (N = 126, 17.3 ± 0.87 years, 55.6% female). Cosinor models found support for robust diurnal rhythms in positive, but not negative, affect. The overall modeled positive affect rhythm had an acrophase at 3:39 PM, a mesor of 9.77, and an amplitude of 1.61. Later circadian timing was associated with later acrophase in positive affect rhythms across the following measures: circadian preference (3:00 PM vs 4:20 PM, p < .001), chronotype (3:20 PM vs 4:11 PM, p = .014), and actigraphy-based midsleep (3:08 PM vs 4:16 PM, p = .014). We did not find significant associations between circadian phase (dim light melatonin onset) and positive affect rhythms. We also explored weekday-weekend differences in positive affect rhythms, finding significantly higher mesor (9.71 vs 9.99, p = .004) and lower amplitude (1.69 vs 1.26, p = .008) on the weekends than weekdays. In sum, compared to their peers, adolescents with later sleep and circadian timing experience a delayed peak in positive affect during the day, which may have consequences for behavioral activation and depressed mood. These findings underscore the importance of considering the role of sleep and circadian factors in affective processes during adolescence.

Temperature regulation across the menstrual cycle follows predictable rhythmic changes driven by reproductive hormones, particularly the thermogenic effect of progesterone in the luteal phase. While basal body temperature has long been used to identify ovulatory cycles, it is less clear how detailed features of the temperature rhythm, including its strength (amplitude) and timing (phase), relate to the likelihood of conception, especially when accounting for individual variability in cycle length and age. Here, we aimed to examine associations between menstrual temperature rhythm characteristics and conception likelihood using both between-person and within-person analyses. We analyzed daily temperature data from 423 women (19-40 years) contributing 4682 cycles, who were participants in a multi-country study about fertility conducted between 1992 and 1996 ("Fertili" dataset). Cycle-level temperature fluctuations were modeled using linear mixed-effects models (GLMMs) with cosine and sine terms scaled to each cycle's length, from which amplitude and phase parameters were derived. At the level of consecutive cycle-series (sessions), GLMMs assessed whether rhythm features, mean temperature, cycle length, cycle regularity, and age predicted conception. Within-person analyses compared pre-conceptive and non-conceptive cycles from the same individual, restricted to cycles with sexual intercourse during the fertile window. Temperature showed a robust oscillatory pattern across the menstrual cycle. At the session level, higher mean temperature was associated with greater conception likelihood in the pre-conceptive cycles, and phase in temperature rhythms tended to be beneficial, particularly in longer cycles. A 3-way interaction revealed that conception was most likely in cycles following shorter cycles (≤35 days) when temperature rhythms were both high in amplitude and well-timed in phase, whereas in longer cycles, rhythm timing appeared to play a larger role than amplitude alone. Within-person comparisons showed that larger temperature phase occurred more often in pre-conceptive cycles than in cycles not followed by conception. Both the magnitude and timing of menstrual temperature rhythms carry information about potential for conception beyond the detection of a post-ovulatory rise. Conception appears most likely when strong rhythmicity aligns optimally with the fertile window in typical length cycles.

Night shift work may alter the gut microbiome through mechanisms involving circadian misalignment, sleep disturbance, and changes in dietary behavior. However, existing studies on this topic have been limited in sample size and scope. We analyzed stool samples from 240 participants (mean age 42 years, 80% women), of whom 53% were night shift workers. Gut microbiota composition was assessed using 16S rRNA gene sequencing to derive measures of relative abundance, alpha diversity, and beta diversity. Associations between night shift work and microbial composition and alpha diversity were examined using generalized linear models with a Gamma distribution and log link for alpha diversity and Aitchison distance for beta diversity. The effect of night shift work on microbiome genera abundance was evaluated using MaAsLin2 analysis. Models were adjusted for age, sex, and educational level. We also explored potential interactions by sleep quality, diet, and chronotype. There were no overall significant differences in alpha or beta diversity between day and night shift workers, but participants with less than 15 years of night work showed slightly higher Abundance-based Coverage Estimator than non-night workers. Interaction with sleep quality was observed (p-value: 0.01). Among participants with poor sleep quality, night shift work was significantly associated with lower alpha diversity (exp(β): 0.93, 95% CI: 0.87-0.99, p-value: 0.02). Day shift workers showed high relative abundance of Ruminococcus, while night shift workers had increased Escherichia-Shigella at descriptive level, none of which remain statistically significant after false discovery rate. Our findings indicate that night shift work may influence gut microbiome diversity, especially in individuals with poor sleep quality. Future research should explore the long-term health consequences of these microbial changes.

The infant gut microbiome is a dynamic ecosystem, and it is key to early development, immune maturation, and overall health. Recent insights reveal that the gut microbiota undergoes changes across the 24-h day, raising the possibility that it may act as a "zeitgeber," supporting the host's sleep-wake organization. Despite its importance, timing factors influencing microbiome composition are poorly understood, limiting its use as a health indicator. This study investigates the relationship between stool dynamics (defecation interval, time of sampling), sleep pressure (interval since last sleep), meal timing, and gut microbial composition. Stool samples from 198 healthy infants, aged 3 to 31 months, were analyzed to assess microbial diversity, richness evenness, and abundance. Our findings reveal that longer intervals between bowel movements are associated with increased microbial diversity, evenness, and richness. Stool timing is associated with shifts in microbial composition, especially in younger infants, indicating diurnal microbial fluctuations to become more stable as infants mature. Longer periods of wakefulness were associated with increased microbial diversity in early infancy, although this effect appeared to diminish with age. Feeding schedules had limited effects on the gut microbiome. Longer fasting before sampling showed no significant associations with most microbial parameters, except for a positive association with microbial richness. At the phylum level, results indicate that infant gut microbial composition is influenced by behavior and physiology. Longer intervals between bowel movements were associated with shifts in bacterial abundance, with Proteobacteria decreasing and Actinobacteria increasing. In addition, later stool sampling times revealed higher Actinobacteria levels, and longer fasting was associated with reduced Bacteroidetes. Sleep pressure showed a trend effect with Firmicutes displaying a slight decrease in infants who had been awake longer. Our findings underscore the importance of time-based factors on infant gut microbiome composition.