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Light at night increases body mass by shifting the time of food intake
Abstract
The global increase in the prevalence of obesity and metabolic disorders coincides with the increase of exposure to light at night (LAN) and shift work. Circadian regulation of energy homeostasis is controlled by an endogenous biological clock that is synchronized by light information. To promote optimal adaptive functioning, the circadian clock prepares individuals for predictable events such as food availability and sleep, and disruption of clock function causes circadian and metabolic disturbances. To determine whether a causal relationship exists between nighttime light exposure and obesity, we examined the effects of LAN on body mass in male mice. Mice housed in either bright (LL) or dim (DM) LAN have significantly increased body mass and reduced glucose tolerance compared with mice in a standard (LD) light/dark cycle, despite equivalent levels of caloric intake and total daily activity output. Furthermore, the timing of food consumption by DM and LL mice differs from that in LD mice. Nocturnal rodents typically eat substantially more food at night; however, DM mice consume 55.5% of their food during the light phase, as compared with 36.5% in LD mice. Restricting food consumption to the active phase in DM mice prevents body mass gain. These results suggest that low levels of light at night disrupt the timing of food intake and other metabolic signals, leading to excess weight gain. These data are relevant to the coincidence between increasing use of light at night and obesity in humans.
... However, environmental factors, such as light exposure at night, have also been implicated in the pathogenesis of obesity [1]. In recent decades, the global rise in obesity prevalence has coincided with increased exposure to light at night [2,3]. The availability of artificial light has substantially changed the light environment, especially during night hours, enabling non-stop economic activities. ...
... In a cross-sectional study, night shift workers had shorter sleep durations and were almost three times more likely to have abdominal obesity, independent of age and gender, compared to day shift workers [5]. Rodent studies have shown that chronic light exposure at night increases susceptibility to weight gain and/or fat accumulation in lean mice [3,6,7], while exaggerating adipose tissue inflammation in a diet-induced obesity model of mice [8]. Although the mechanisms behind night-time light exposure and obesity remain largely elusive, accumulating evidence suggests that disrupted circadian (~24 h) rhythms, such as erratic eating patterns, play a crucial role in mediating metabolic dysfunction [3,8]. ...
... Rodent studies have shown that chronic light exposure at night increases susceptibility to weight gain and/or fat accumulation in lean mice [3,6,7], while exaggerating adipose tissue inflammation in a diet-induced obesity model of mice [8]. Although the mechanisms behind night-time light exposure and obesity remain largely elusive, accumulating evidence suggests that disrupted circadian (~24 h) rhythms, such as erratic eating patterns, play a crucial role in mediating metabolic dysfunction [3,8]. ...
Time-restricted feeding (TRF) has emerged as a promising dietary approach for improving metabolic parameters associated with obesity. However, it remains largely unclear whether TRF offers benefits for obesity related to exposure to light at night. This study examined whether lean and obese mice under chronic light exposure could benefit from TRF intervention. Six-week-old C57BL/6 male mice were fed either a low-fat diet or a high-fat diet under a 12 h light/12 h dark cycle for 6 weeks. They were then divided into three subgroups: control light, chronic 24 h light, and chronic light with a daily 10 h TRF. Chronic light exposure led to increased weight gain and higher expression of inflammatory and fibrotic markers in the adipose tissue of both lean and obese mice. It also increased hepatic triglyceride content in mice, regardless of their weight status. TRF protected both lean and obese mice from weight gain, normalized inflammatory and fibrotic gene expression, and reduced adipose tissue collagen and liver triglyceride accumulation caused by light exposure alone or in combination with obesity. These results suggest that TRF could have clinical implications for preventing obesity associated with night shift work, regardless of current weight status.
... (1) No changes in serum corticosterone levels and hippocampal glucocorticoid receptor expression were observed after ALAN (5 lx; 3 days) in female and male Swiss Webster mice during both the light and the dark phases of the day [89]. Even longer exposure to ALAN (5 lx; 3-7 weeks) did not affect the corticosterone levels in mice in the light [6,29] and the dark [29] phases of the day. (2) Suppression of the diurnal rhythm of serum cortisol after ALAN (5 lx; 1 week) was observed in adult female Siberian hamsters [7]. ...
... (1) No changes in serum corticosterone levels and hippocampal glucocorticoid receptor expression were observed after ALAN (5 lx; 3 days) in female and male Swiss Webster mice during both the light and the dark phases of the day [89]. Even longer exposure to ALAN (5 lx; 3-7 weeks) did not affect the corticosterone levels in mice in the light [6,29] and the dark [29] phases of the day. (2) Suppression of the diurnal rhythm of serum cortisol after ALAN (5 lx; 1 week) was observed in adult female Siberian hamsters [7]. ...
... For example, in adult female Siberian hamsters (crepuscular), ALAN (5 lx; one week) did not alter locomotor activity [7]. Similarly, in male Swiss-Webster mice (5 lx; 8 weeks) and diurnal male Nile grass rats (5 lx; 3 weeks), ALAN did not affect locomotor activity [27,29]. Moreover, ALAN did not affect total daily wheel running in Swiss-Webster mice, but some animals became arrhythmic [28]. ...
Artificial light at night (ALAN) affects most of the population. Through the retinohypothalamic tract, ALAN modulates the activity of the central circadian oscillator and, consequently, various physiological systems, including the cardiovascular one. We summarised the current knowledge about the effects of ALAN on the cardiovascular system in diurnal and nocturnal animals. Based on published data, ALAN reduces the day-night variability of the blood pressure and heart rate in diurnal and nocturnal animals by increasing the nocturnal values of cardiovascular variables in diurnal animals and decreasing them in nocturnal animals. The effects of ALAN on the cardiovascular system are mainly transmitted through the autonomic nervous system. ALAN is also considered a stress-inducing factor, as glucocorticoid and glucose level changes indicate. Moreover, in nocturnal rats, ALAN increases the pressure response to load. In addition, ALAN induces molecular changes in the heart and blood vessels. Changes in the cardiovascular system significantly depend on the duration of ALAN exposure. To some extent, alterations in physical activity can explain the changes observed in the cardiovascular system after ALAN exposure. Although ALAN acts differently on nocturnal and diurnal animals, we can conclude that both exhibit a weakened circadian coordination among physiological systems, which increases the risk of future cardiovascular complications and reduces the ability to anticipate stress.
... In a human experiment, circadian misalignment protocols based on using two 8-d laboratory schedules in healthy men induced glucose tolerance decreases in the evening, along with decreased insulin sensitivity and pancreatic β-cell function [10]. The mechanisms underlying this association have been studied using animal models with aberrant lighting conditions, such as constant light, dim light at night [11], shortened periods of light-dark cycles (e.g., 10 h light -10 h dark) [8], or chronic jet lag (CJL) [12]. The CJL protocol involves frequent shifts of advancing light/dark cycles by 6-8 h every 2-7 days and induces dysregulation of circadian rhythms, metabolism, and behaviors in rodents [12][13][14][15]. ...
... Overall, this research highlights significant differences between the sexes in regard to how CJL impacts the circadian clock and metabolism, emphasizing the important role of testosterone in regulasting these processes in males. signs of increased weight and glucose intolerance without changes in total daily food intake under aberrant lighting conditions [8,11,12]. Therefore, these findings highlight the need for further research investigating the sex-specific effects of CJL on metabolic health. ...
Background
The circadian clock integrates external environmental changes into the internal physiology of organisms. Perturbed circadian clocks due to misaligned light cycles increase the risk of diseases, including metabolic disorders. However, the effects of sex differences in this context remain unclear.
Methods
Circadian misalignment was induced by a chronic jet lag (CJL) shift schedule (light-on time advanced by 6 h every 2 days) in C57BL/6N male and female mice. Core body temperature and activity rhythms were recorded using a nano tag, and the gene expression rhythms of clock and clock-controlled genes in the liver and adrenal glands were analyzed using qPCR. Glucose metabolism and insulin response were evaluated using glucose tolerance, insulin sensitivity, and glucose response assays. Castration and testosterone replacement were performed to assess the fundamental role of testosterone in male phenotypes under CJL.
Results
Under CJL treatment, male mice exhibited increased weight gain, whereas females exhibited decreased weight gain compared to that of the respective controls. CJL treatment induced a lower robustness of circadian rhythms in core body temperature and a weaker rhythm of clock gene expression in the liver and adrenal glands in females, but not in males. Only male mice exhibited glucose intolerance under CJL conditions, without the development of insulin resistance. Castrated mice without testosterone exhibited decreased weight gain and reduced robustness of body temperature rhythm, as observed in intact females. Testosterone replacement in castrated mice recovered the CJL-induced weight gain, robustness of temperature rhythm, and glucose intolerance observed in intact males.
Conclusions
Significant sex-based differences were observed in circadian clock organization and metabolism under CJL. Testosterone plays a crucial role in maintaining the circadian clock and regulating CJL metabolism in males.
... In contrast, light at night in rats decreases nighttime sympathetic signaling to decrease the amplitude of these rhythms. Studies show that low or dim light levels at night dampen the amplitude of rhythmic feeding behavior and activity in mice 7,16 . We found that rhythmic feeding behavior modifies the amplitude and acrophase of the day-night heart rate and blood pressure rhythms by altering autonomic signaling 17,18 . ...
... Time-restricted feeding to the dLAN cycle did not restore the amplitude of activity rhythms Light at night exposure can change locomotor activity in diurnal and nocturnal animals 7,16,34 . We found that exposing mice to dLAN reduced the amplitude of 24-hour activity rhythms in female mice and caused a reduction in activity during the dark cycle in both female and male mice. ...
Background: Light input to the suprachiasmatic nucleus entrains circadian rhythms in physiology and behavior to the day-night cycle. Exposure to light at night in people is associated with cardiometabolic disease. Pre-clinical studies show that artificial light at night, including at very low levels, disrupts day-night rhythms in activity, feeding behavior, heart rate, and blood pressure dipping.
Hypothesis: Dim light at night (dLAN) disrupts day-night rhythms in feeding behavior to blunt day-night rhythms in autonomic input to the heart and blood pressure dipping.
Methods: Mice (n=5-6/sex) in thermoneutral housing were implanted with telemetry probes to record heart rate, blood pressure, and core body temperature. Autonomic input to the heart was assessed by measuring heart rate and subtracting the temperature-dependent changes in the heart rate after pharmacological inhibition of muscarinic and β-adrenergic receptor activation. Mice were housed in 12 h light: 12 h dark cycles (LD, 200 lux: 0 lux) with ad libitum access to food (LD-ALF), subjected to 12 h light: 12 h dLAN cycles (dLAN-ALF; 200 lux: 5 lux) for two weeks, and then feeding was time-restricted (not calorically restricted) to the dLAN cycle (dLAN-RF). Data were extracted from Ponemah and Clocklab, and statistical analysis was done using GraphPad PRISM software.
Results: Compared to LD-ALF mice, dLAN-ALF mice showed reduced amplitudes in day-night activity, feeding, heart rate, and blood pressure rhythms, with males more affected than females (p<0.001). dLAN-ALF male and female mice had decreased amplitudes in the day-night rhythms in autonomic input to the heart. In addition, dLAN-ALF male mice had less blood pressure dipping. dLAN-RF normalized autonomic input to the heart and heart rate in male and female mice (p<0.05, p<0.01, respectively). dLAN-RF also improved blood pressure dipping in male mice (p<0.001). dLAN-RF did not normalize activity rhythms.
Conclusion: dLAN disrupts day-night rhythms in activity, feeding, heart rate, and blood pressure dipping in mice, with males being more impacted. Time-restricted feeding to the dLAN cycle normalizes autonomic input to the heart and blood pressure dipping. These data suggest that time-restricted feeding counteracts the light-at-night-induced circadian disruption of cardiovascular function.
... In contrast, light at night in rats decreases nighttime sympathetic signaling to decrease the amplitude of these rhythms. Studies show that low or dim light levels at night dampen the amplitude of rhythmic feeding behavior and activity in mice 7,16 . We found that rhythmic feeding behavior modifies the amplitude and acrophase of the day-night heart rate and blood pressure rhythms by altering autonomic signaling 17,18 . ...
... Time-restricted feeding to the dLAN cycle did not restore the amplitude of activity rhythms Light at night exposure can change locomotor activity in diurnal and nocturnal animals 7,16,34 . We found that exposing mice to dLAN reduced the amplitude of 24-hour activity rhythms in female mice and caused a reduction in activity during the dark cycle in both female and male mice. ...
Shift work and artificial light at night disrupt the entrainment of endogenous circadian rhythms in physiology and behavior to the day-night cycle. We hypothesized that exposure to dim light at night (dLAN) disrupts feeding rhythms, leading to sex-specific changes in autonomic signaling and day-night heart rate and blood pressure rhythms. Compared to mice housed in 12-hour light/12-hour dark cycles, mice exposed to dLAN showed reduced amplitudes in day-night feeding, heart rate, and blood pressure rhythms. In female mice, dLAN reduced the amplitude of day-night cardiovascular rhythms by decreasing the relative sympathetic regulation at night, while in male mice, it did so by increasing the relative sympathetic regulation during the daytime. Time-restricted feeding to the dim light cycle reversed these autonomic changes in both sexes. We conclude that dLAN induces sex-specific changes in autonomic regulation of heart rate and blood pressure, and time-restricted feeding may represent a chronotherapeutic strategy to mitigate the cardiovascular impact of light at night.
... Conditions such as shift work or electronic device use that expose individuals to ALAN have been associated with increased sedentary behavior [101] and decreased opportunities for physical activity [102]. Additionally, the timing of food intake, a critical factor in energy metabolism, is often delayed under ALAN exposure, leading to a higher risk of obesity even with similar total daily caloric intake, as shown in both mice [103] and human studies [104,105]. ...
... Having dinner later has been associated with both impaired glucose tolerance [84] and increased T2DM risk [85] compared to earlier dinner times. An experimental study demonstrated that exposure to ALAN is associated with obesity, potentially due to a shift in the timing of food intake, even when caloric intake and total daily activity remain constant [103]. Additionally, individuals with an evening chronotype are known to have a higher prevalence of night-eating syndrome [125]. ...
The widespread and pervasive use of artificial light at night (ALAN) in our modern 24-hour society has emerged as a substantial disruptor of natural circadian rhythms, potentially leading to a rise in unhealthy lifestyle-related behaviors (e.g., poor sleep; shift work). This phenomenon has been associated with an increased risk of type 2 diabetes mellitus (T2DM), which is a pressing global public health concern. However, to date, reviews summarizing associations between ALAN and T2DM have primarily focused on the limited characteristics of exposure (e.g., intensity) to ALAN. This literature review extends beyond prior reviews by consolidating recent studies from 2000 to 2024 regarding associations between both indoor and outdoor ALAN exposure and the incidence or prevalence of T2DM. We also described potential biological mechanisms through which ALAN modulates glucose metabolism. Furthermore, we outlined knowledge gaps and investigated how various ALAN characteristics beyond only light intensity (including light type, timing, duration, wavelength, and individual sensitivity) influence T2DM risk. Recognizing the detrimental impact of ALAN on sleep health and the behavioral correlates of physical activity and dietary patterns, we additionally summarized studies investigating the potential mediating role of each component in the relationship between ALAN and glucose metabolism. Lastly, we proposed implications of chronotherapies and chrononutrition for diabetes management in the context of ALAN exposure.
... Light pollution emerging from artificial light at night (ALAN) is increasing worldwide [1]. Lighting technology has developed solutions offering energy-saving illumination of short-wavelength (SWL) light as light-emitting diodes (LEDs), among other technologies. ...
... A similar mass gain in response to ALAN exposure was also demonstrated in mice showing a wavelength dependent with the strongest effect at the SWL of the spectrum [30]. In mice, ALAN exposure can induce mass gain by altering the animal feeding behavior, e.g., shifting the typical timing of food intake [1,17]. In birds, ALAN can extend the bird's activity by advancing activity onset and delaying activity offset in an intensity direct dose-dependent manner [15]. ...
Short-wavelength artificial light at night is increasingly being associated with health and ecological risks. The negative impact of this relatively new source of pollution has been studied intensively in wild birds but to a much lesser extent in captive conspecifics. Using an avian model, our objective was to evaluate the effects of short-wavelength (200 lux at 460 nm) lighting on the body mass and reproductive success of Budgerigars (Melopsittacus undulatus) under captive conditions. Birds were maintained under a naturally increasing photoperiod from March to June, with one daily artificial light at night exposure of increasing duration (0, 30, 60, and 90 min) in the middle of the dark period. During the experiments, birds were monitored monthly for body mass, number of eggs laid, hatching success, and melatonin sulfate levels in droppings. Artificial light at night increased body mass and decreased melatonin sulfate levels as well as the number of eggs and hatching success in a duration dose-dependent manner. Our findings provide further evidence of the potential adverse impact of artificial light at night on captive birds and advocate the need for effective controlling measures for light pollution.
... Interestingly, nocturnal rodents typically consume substantially more food at night (Olsen et al., 2017;Challet, 2019). Exposure to excessive light in the dark phase is associated with aberrant food intake and body mass (Fonken et al., 2010;Borniger et al., 2014), suggesting that light may regulate feeding. However, long-term light manipulations often result in a disrupted circadian clock, which is a well-known cause of metabolic disorders (Rudic et al., 2004;Turek et al., 2005;Kettner et al., 2015). ...
... Light is a powerful modulator of many biological activities, including mood, locomotion, sleep, arousal, and glucose metabolism (Vandewalle et al., 2009;LeGates et al., 2014;Meng et al., 2023). Dark cycle light exposure is also relevant to eating abnormalities (Fonken et al., 2010). However, chronic light stimulation often leads to a shift in circadian rhythmicity, which is closely associated with metabolic disruptions (Rudic et al., 2004;Turek et al., 2005;Kettner et al., 2015). ...
Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb → 5-HT DRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.
Significance statement Feeding behavior is influenced by a myriad of sensory inputs, but the impact of light exposure on feeding regulation has remained enigmatic. Here, we showed that light exposure diminishes food intake across both nocturnal and diurnal species. Delving deeper, our findings revealed that the LHb → 5-HT DRN neural circuit plays a pivotal role in mediating light-induced anorexia in mice. These discoveries not only enhance our comprehension of the intricate neuronal mechanisms governing feeding in response to light but also offer insights for developing innovative strategies to address obesity and eating disorders.
... Dim light at night is an issue of public health relevance, and it can change how behaviors are synchronized to the day in both humans and animals (29,149). In mice, dim light at night redistributes food intake into the normal rest phase, and the final body weight gain is correlated with the calories consumed at the inappropriate time (45). Importantly for translation, dim light at night impairs glucose tolerance in both nocturnal and diurnal rodents (85,103) and humans (86). ...
... When animals eat can have as much effect on metabolic health as what they eat: mistimed food reliably compromises metabolism (10,21,45,121,127) (Figure 3c). The power of food timing to organize behavior has been evident for a long time. ...
The time of day that we eat is increasingly recognized as contributing as importantly to overall health as the amount or quality of the food we eat. The endogenous circadian clock has evolved to promote intake at optimal times when an organism is intended to be awake and active; but electric lights and abundant food allow eating around the clock with deleterious health outcomes. In this review, we highlight literature pertaining to the effects of food timing on health, beginning with animal models and then translation into human experiments. We emphasize the pitfalls and opportunities that technological advances bring in bettering understanding of eating behaviors and their association with health and disease. There is great promise for restricting the timing of food intake both in clinical interventions and in public health campaigns for improving health via nonpharmacological therapies.
... In mouse studies, feeding animals only during the rest (light) phase resulted in greater weight gain compared to feeding them during the active (dark) phase (55). A replication and extrapolation of this study showed that mice gained even more weight under constant light conditions, but not when restricting the food intake to their "biological night" (56). Additionally, time-restricted feeding was found to compensate for the adverse effects of an unhealthy (high-fat) diet (57). ...
... However, in the modern era, light conditions changed with the development of artificial lighting, enabling activities around the clock, e.g., socializing via lightemitting devices, or the possibility of commerce, production, and access to 24-h services, and therefore also leading to shifts in meal timing (170). A possible consequence of this is that light at night and the corresponding longer active compared to rest phase intervals have led to an increase in food intake and therefore excessive weight gain, as shown in rodent studies (56). A significant interaction between food and meal timing was previously described due to an influence of meal timing on sleep timing, and even the sleep timing influence was stronger than the meal timing influence regarding parameters of food intake (171). ...
Meal timing emerges as a crucial factor influencing metabolic health that can be explained by the tight interaction between the endogenous circadian clock and metabolic homeostasis. Mistimed food intake, such as delayed or nighttime consumption, leads to desynchronization of the internal circadian clock and is associated with an increased risk for obesity and associated metabolic disturbances such as type 2 diabetes and cardiovascular diseases. Conversely, meal timing aligned with cellular rhythms can optimize the performance of tissues and organs. In this review, we provide an overview of the metabolic effects of meal timing and discuss the underlying mechanisms. Additionally, we explore factors influencing meal timing, including internal determinants such as chronotype and genetics, as well as external influences like social factors, cultural aspects, and work schedules. This review could contribute to defining meal-timing-based recommendations for public health initiatives and developing guidelines for effective lifestyle modifications targeting the prevention and treatment of obesity and associated metabolic diseases. Furthermore, it sheds light on crucial factors that must be considered in the design of future food timing intervention trials.
... Exposure to constant light has been shown to disrupt the circadian rhythms and lead to depressive and anxiety-like behaviors (Fonken & Nelson, 2014;Tapia-Osorio, Salgado-Delgado, Angeles-Castellanos, & Escobar, 2013). Furthermore, circadian disruption caused by constant light housing is associated with altered patterns of food intake and elevated plasma corticosterone levels, and is utilized as an animal model of chronic stress (Fonken et al., 2010;Welberg, Thrivikraman, & Plotsky, 2006;Castelhano-Carlos & Baumans, 2009). ...
... It is well known that circadian rhythms play a crucial role in the physiological processes associated with energy metabolism and energy balance. Thus disruptions in circadian rhythms can impact dietary intake and energy metabolism, as evidenced by a study demonstrating that circadian disruption by light at night in mice led to changes in food intake and activity, which contributed to weight gain and metabolic dysfunction (Fonken et al., 2010). Additionally, recent findings indicated that olfactory stimulation by O. fragrans suppressed the intracerebral secretion of orexin, a neuropeptide that regulates sedation and appetite, thereby leading to a decrease in dietary intake and body weight (Hozumi et al., 2017;Qian et al., 2023). ...
This study evaluated the effects of inhaling Osmanthus fragrans var. aurantiacus (OFA) extracts in Sprague-Dawley (SD) rats experiencing chronic stress. Rats were exposed to restraint stress or circadian disruption and were inhaled either distilled water or OFA extracts. Electronic nose (E-nose) analysis identified 35 volatile aromatic compounds (VACs) in OFA extracts. Chronic stress led to a decrease in body weight initially, serotonin concentration, and the weights of the liver, kidneys, and fat pads. Additionally, circadian disruption increased melatonin levels and decreased cholesterol concentrations. Inhalation of OFA increased dietary intake during the early phase and restored the tissue weights that have changed by chronic stress. Furthermore, it led to an increase in melatonin levels and changes in cholesterol levels. Taken together, our results indicate that OFA inhalation improves physiological changes caused by chronic stress through regulating dietary intake, restoring tissue weights, and modulating hormone and cholesterol levels.
... Studies on rodents have shown that consuming a high-fat diet during the rest phase (the light phase for nocturnal rodents) leads to more significant weight gain than does consuming the same diet during the active phase (22). Furthermore, nocturnal light exposure increases body weight by altering the timing of food intake (23). In addition, many previous studies have suggested that disruptions in circadian rhythms may affect the endocrine system, potentially leading to obesity, DM and cardiovascular disease (24)(25)(26). ...
Thyroid function is closely linked to circadian rhythms, but the relationship between the frequency of night eating and thyroid function remains unclear. Our study aimed to investigate the association between night eating frequency and its impact on thyroid function and sensitivity. This study included 6093 participants from the U.S. National Health and Nutrition Examination Survey (2007–2012). Night eating behavior was assessed through 24-hour dietary recall, with night eating frequency calculated on the basis of food intake between 10:00 PM and 4:00 AM. The thyroid hormone indices examined included T3, T4, FT3, FT4, TSH, TGA, Tg, and TPOAb, whereas thyroid hormone sensitivity was assessed via indices such as the FT3/FT4, TSHI, TT4RI, and TFQI. The associations between night eating frequency and thyroid function were analyzed via weighted univariate and multivariate linear regression analyses. Subgroup analyses and interaction test analyses were also employed to test this correlation. Compared with individuals who did not eat at night, those who ate more frequently at night had higher levels of Tg (OR 1.223 [95% CI 1.048, 1.429], p trend=0.015) but lower levels of T3 (OR 0.728 [95% CI 0.611, 0.868], p trend=0.235) and TPOAb (OR 0.728 [95% CI 0.611, 0.868], p trend=0.235). Subgroup analysis indicated that this association between Tg and night eating was stronger in the DM group (Tg: OR 1.49 [95% CI 1.15, 1.93]), p interaction=0.022) and that the association between TPOAb and night eating was stronger in the group without DM (TPOAb: OR 0.9 [95% CI 0.82, 0.97]), p interaction=0.003). Our findings suggest a significant association between night eating frequency and thyroid function. However, no statistically significant differences were found in thyroid sensitivity based on night eating frequency. Despite these findings, the hormone fluctuations observed were within normal clinical ranges. Further rigorously designed studies are needed to establish a causal relationship between night eating frequency and thyroid function.
... In mice, artificial light at night (ALAN) increases BMI and decreases glucose tolerance, in parallel with a shift in the eating time for the light phase, independently of an increase in calorie intake or physical activity [138]. ALAN exposure disrupted the core circadian rhythms in the central clock changing the mice's feeding behaviors, and in the peripheral clocks, particularly the liver and adipose tissue, resulting in weight gain despite no change in total daily food intake [139,140]. ...
Earth’s rotation around its axis has pressured its inhabitants to adapt to 24 h cycles of day and night. Humans adapted their own circadian rhythms to the Earth’s rhythms with a light-aligned awake–sleep cycle. As a consequence, metabolism undergoes drastic changes throughout the circadian cycle and needs plasticity to cope with opposing conditions in the day (when there is an increase in energy demands and food availability), and during the night (when prolonged fasting couples with cyclic changes in the energy demands across the sleep stages). In the last century, human behavior changed dramatically with a disregard for the natural circadian cycles. This misalignment in sleep and eating schedules strongly modulates the metabolism and energy homeostasis, favoring the development of obesity, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review summarizes the effects of circadian disruption, with a particular focus on the feeding and sleep cycles in the development of MASLD and hepatocellular carcinoma.
... This is mainly attributed to a reduction of melatonin, which is not only a sleep-inducing, antioxidant, anticonvulsant, and antiinflammatory molecule, but also a hormone involved in body repair during sleep and key control of hormonal and immune activities throughout the body. In mice, illumination during the dark phase increases body weight and impairs glucose tolerance without affecting daily calorie intake or activity [14]. A prospective study conducted on 678 elderly participants with no evidence of diabetes at baseline showed that light at night (5 lux) was associated with J o u r n a l P r e -p r o o f increased incidence of type 2 diabetes [15]. ...
... Evidence for the importance of food timing for obesity comes from animal models (8)(9)(10) as well as observational (11,12) and experimental (13,14) studies in humans, although not all studies are consistent (15,16) . Previous observational studies linking late eating with higher obesity risk revealed that food timing per se might alter body weight without a significant difference in energy intake and expenditure (17,18) . ...
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.
... Previous studies also showed a reduction in the activity of nocturnal rodents, such as M. musculus and M. minutoides, when they were presented with LAN in the laboratory (Shuboni et al., 2015;Viljoen and Oosthuizen, 2023). They can also show signs of depressive behaviours, reduced learning and memory (Fonken et al., 2012) and altered times of food consumption (Fonken et al., 2010). ...
Multimammate mice are prolific breeders, can cause significant agricultural damage, and are reservoir hosts for a number of pathogens. They are nocturnal and given their success in urbanised rural environments, we were interested in how they would respond to increasingly bright anthropogenic spaces. We evaluated the locomotor activity of southern multimammate mice (Mastomys coucha), under four treatments: in an outdoor enclosure with natural light and temperature fluctuations, in a laboratory under a standard light regime, and two artificial light at night (ALAN) regimes (2 Lux) of varying proximity. The study animals remained nocturnal for the duration of the experiments. They were more active under the laboratory conditions with lower daytime light levels compared to the outdoor treatment but reduced their activity under ALAN. When the night light originated remotely, activity levels decreased by more than 50%, whereas under direct ALAN from above the cages, there was a 75% decrease in activity. The onset of activity was later during the two LAN treatments. We concluded that Mastomys coucha is strongly averse to light and show severe behavioural and circadian responses to light at night. We predict that it is unlikely that Mastomys will flourish in cities, but that they could thrive in and around dark urbanised refugia.
... A similar disruption in feeding pattern in terms of the duration and frequency, and increased body fattening and weight gain has been reported in both nocturnal and diurnal higher vertebrates, e.g. rodents and song birds [4,13,15,16,32,[47][48][49]. Notably, the consumption of calories late at night has also been found associated with obesity in humans [50]. ...
This experiment investigated the effects of an ecologically relevant level of dim light at night (dLAN) on behavior, physiology and fat metabolism associated gene expressions in central and peripheral tissues of adult male zebra finches that were hatched and raised in 12:12 h LD cycle (Ev, day = 150 ± 5 lx; Ev, night = 0 lx) at 22 ± 2 °C temperature. Half of the birds (n = 8) were maintained on LD cycle and temperature, as before (control), to the other half of birds the 12 h dark period was dimly illuminated at ~ 5 lx (dim light at night, dLAN; Ev, day = 150 ± 5 lx; Ev, night = ~ 5 lx) for 6 weeks. The exposure to dLAN altered the 24 h activity and feeding patterns with enhanced activity and feeding at night. Birds under dLAN fattened and gained weight, and had higher night glucose levels. Concurrently, a negative effect of dLAN was found on mRNA expression of ppar-alpha and cd36 genes involved in the fat metabolism in the hypothalamus, intestine, liver and muscle. These results suggest a more global effect of dLAN exposure on obesity and perhaps long-term health risks due to obesity-related complications to diurnal animals including humans inhabiting an urbanized environment. Graphical abstract
... Moreover, arti cial lighting has signi cantly altered nighttime environments [20]. Exposure to arti cial light at night disrupts sleep/wake cycles and circadian functions, affecting nighttime hormone production and secretion, which may induce various diseases [21][22][23][24]. Therefore, in addition to shift work, factors like non-work-related light exposure at night, sleep disorders, and insu cient sleep are also key in studying circadian rhythm disruption. ...
Objective : To construct comprehensive indicators of circadian rhythm disorder (CICRD) and explore the interaction effects between CICRD and circadian rhythm-related gene polymorphisms (SNPs) on the risk of type 2 diabetes mellitus (T2DM). Methods : Baseline data were collected from the Xingtai coal site of the Occupational Cohort Study on Health Effects. A cross-sectional study was initially conducted, involving 4,070 coal miners who underwent occupational health examinations during 2017 and 2018. We performed factor analysis to construct the CICRD and logistic regression models to estimate the association between CICRD and T2DM. Restricted cubic spline (RCS) function was used to determine the exposure-response association. In the subsequent case-control analysis, 424 cases and 464 controls were randomly selected from 3,878 male coal miners. Logistic regression model was employed to examine the association between selected SNPs and T2DM. Gene-gene and gene-environment interactions were evaluated using log-linear models and the generalized multifactor dimensionality reduction (GMDR) method. Results: The CICRD constructed by factor analysis explained 79.771% of the original variance. After adjusting for confounding factors, CICRD was associated with the increased risk of T2DM. Variants at rs10830963 in the MTNR1B gene, rs7958822 in the BMAL2 gene, and rs11605924 in the CRY2 gene were associated with the increased risk of T2DM. Interactions between rs10830963 in the MTNR1B gene and rs11605924 in the CRY2 gene ( RERI : 0.2; AP : 0.46), as well as between rs7958822 in the BMAL2 gene and rs11605924 in the CRY2 gene ( RERI : 1.55; AP : 0.56), were associated with increased risk of T2DM. A CICRD score ≥ 0.2782 combined with high-risk genotypes at four SNPs (rs10830963 and rs1387153 in MTNR1B, rs7958822 in BMAL2, and rs11605924 in CRY2) was associated with increased risk of T2DM ( P < 0.05). The complex intersection of four-factor interaction model (rs10830963-rs1387153-rs7958822-rs11605924) and five-factor interaction model (rs10830963-rs7950226-rs7958822-rs11605924-CICRD) based on GMDR method interactions increased the risk of T2DM in the full data set ( P < 0.05). Conclusion: An increase in CICRD, along with variants at rs10830963 in the MTNR1B gene, rs7958822 in the BMAL2 gene, and rs11605924 in the CRY2 gene, was associated with an increased risk of T2DM among coal miners. The four-factor model (rs10830963-rs1387153-rs7958822-rs11605924) and the five-factor model (rs10830963-rs7950226-rs7958822-rs11605924-CICRD) exhibited significant high-order interactions associated with an increased risk of T2DM among coal miners.
... Prior studies showed that NTL satellite imagery has been employed to estimate population density 12 , economic growth 13 , Gross Domestic Product 13,14 , urbanization 15 , and so on, all of which bear relevance to COVID-19 transmission dynamics. Furthermore, exposure to more intense NTL has been associated with elevated obesity prevalence 16,17 , and obese individuals may be more prone to severe COVID-19 consequences 18,19 . Some studies have analyzed NTL changes during social distancing periods in several large cities including China and the U.S 10,20 . ...
The COVID-19 pandemic has highlighted the importance of understanding environmental factors in disease transmission. This study aims to explore the spatial association between nighttime light (NTL) from satellite imagery and COVID-19 mortality. It particularly examines how NTL serves as a pragmatic proxy to estimate human interaction in illuminated nocturnal area, thereby impacting viral transmission dynamics to neighboring areas, which is defined as spillover effect. Analyzing 43,199 COVID-19 deaths from national mortality data during January 2020 and October 2022, satellite-derived NTL data, and various environmental and socio-demographic covariates, we employed the Spatial Durbin Error Model to estimate the direct and indirect effect of NTL on COVID-19 mortality. Higher NTL was initially directly linked to increased COVID-19 mortality but this association diminished over time. The spillover effect also changed: during the early 3rd wave (December 2020 – February 2021), a unit (nanoWatts/sr/cm²) increase in NTL led to a 7.9% increase in neighboring area mortality (p = 0.013). In contrast, in the later 7th wave (July – September 2022), dominated by Omicron, a unit increase in NTL resulted in an 8.9% decrease in mortality in neighboring areas (p = 0.029). The shift from a positive to a negative spillover effect indicates a change in infection dynamics during the pandemic. The study provided a novel approach to assess nighttime human activity and its influence on disease transmission, offering insights for public health strategies utilizing satellite imagery, particularly when direct data collection is impractical while the collection from space is readily available.
... 17 Even when dietary intake and physical activity levels are consistent, long-term exposure to ALAN can increase body weight and disrupt glucose production and change. 18 The disruption of circadian rhythms caused by light exposure increases metabolic abnormalities and the risk of obesity and diabetes. As a nationally representative study spanning 162 study sites, the 2010 China Chronic Noncommunicable Disease Surveillance Study included 98 658 participants over 18 years of age who had resided at the current study site for at least 6 months. ...
Background
Artificial light at night (ALAN) is a common phenomenon and contributes to the severe light pollution suffered by more than 80% of the world's population. This study aimed to evaluate the relationship between outdoor ALAN exposure and cardiovascular health (CVH) in patients with diabetes and the influence of various modifiable factors.
Methods
A survey method based on the China Diabetes and Risk Factor Monitoring System was adopted. Study data were extracted for 1765 individuals with diabetes in Anhui Province. Outdoor ALAN exposure (nW/cm²/sr) within 1000 m of each participant's residential address was obtained from satellite imagery data, with a resolution of ~1000 m. Health risk behaviors (HRBs) were measured via a standardized questionnaire. A linear regression model was employed to estimate the relationship between outdoor ALAN, HRBs, and CVH.
Results
Participants' mean age was 59.10 ± 10.0 years. An association was observed between ALAN and CVH in patients with diabetes (β = 0.205) and exercise (β = −1.557), moderated by HRBs, or metabolic metrics. There was an association between ALAN, ALAN, vegetable intake, and CVH.
Conclusions
Exploring the relationship between ALAN exposure and cardiovascular and metabolic health provides policy data for improving light pollution strategies and reducing the risk of cardiovascular and metabolic disease in patients with diabetes.
image
... In humans, cervical SCI could also disrupt the diurnal rhythm of body temperature in chronic phase 33 , and sleep disturbance is common in people with SCI 34 . Dysregulation of the circadian rhythm could affect physiological function, predispose to disease, and worsen outcomes after injury 35,36 . For instance, disruption of the circadian clock by exposure to abnormally timed light after traumatic brain injury in rats increased neuronal death and the volume of cortical lesions, resulting in a worsening of sensorimotor and cognitive impairments 37 . ...
Circadian dysregulation involved in the pathophysiology of spinal cord injury (SCI). Modulation of circadian rhythms hold promise for the SCI treatment. Here, we aim to investigated the mechanism of olfactory ensheathing cells (OEC) in alleviating neuroinflammation via modulating clock gene expression in microglia. In this study, SCI rats were randomly divided into OEC group and vehicle group. At 1 day after the surgery, OECs were intravenously transplanted into OEC group SCI rat, while the rats in vehicle group received culture medium. After 7 days post of OEC transplantation, tissues were collected from the brain (prefrontal cortex, hypothalamus, spinal cord) for PCR, western blotting and immunohistochemistry (IHC) assay at zeitgeber time (ZT) 6, ZT 12, ZT 18, and ZT 24. The roles of OEC in modulating REV-ERBα in microglia were studied by experimental inhibition of gene expression and the co-culture experiment. In the vehicle group, IHC showed a significant increase of Iba-1 expression in the cerebral white matter and spinal cord compared with control group (P < 0.0001 for all comparisons). The expression of Iba-1 was significantly decreased (P < 0.0001 for all comparisons). In the OEC group, the expression of PER 1, PER 2, CLOCK, and REV-ERBα was in a rhythmical manner in both spinal cord and brain regions. SCI disrupted their typical rhythms. And OECs transplantation could modulate those dysregulations by upregulating REV-ERBα. In vitro study showed that OECs couldn’t reduce the activation of REV-ERBα inhibited microglia. The intravenous transplantation of OECs can mediate cerebral and spinal microglia activation through upregulation REV-ERBα after SCI.
... 194) of municipal electricity consumption, increasing the pressure on municipal budgets. Furthermore, correlations between satellite-measured outdoor light and an increased risk of various health conditions 195 including cancer [196][197][198] , obesity 199 and diabetes 200 , as well as negative impacts on people's mental health 201 and sleep quality, have been observed. However, it is difficult to confirm whether a causal relationship exists because numerous environmental parameters correlate with light emissions, which Review article could also be responsible for these health impacts 202 , and satellite observations are an imperfect proxy for true light exposure. ...
... 194) of municipal electricity consumption, increasing the pressure on municipal budgets. Furthermore, correlations between satellite-measured outdoor light and an increased risk of various health conditions 195 including cancer [196][197][198] , obesity 199 and diabetes 200 , as well as negative impacts on people's mental health 201 and sleep quality, have been observed. However, it is difficult to confirm whether a causal relationship exists because numerous environmental parameters correlate with light emissions, which could also be responsible for these health impacts 202 , and satellite observations are an imperfect proxy for true light exposure. ...
Light pollution has increased globally, with 80% of the total population now living under light-polluted skies. In this Review, we elucidate the scope and importance of light pollution and discuss techniques to monitor it. In urban areas, light emissions from sources such as street lights lead to a zenith radiance 40 times larger than that of an unpolluted night sky. Non-urban areas account for over 50% of the total night-time light observed by satellites, with contributions from sources such as transportation networks and resource extraction. Artificial light can disturb the migratory and reproductive behaviours of animals even at the low illuminances from diffuse skyglow. Additionally, lighting (indoor and outdoor) accounts for 20% of global electricity consumption and 6% of CO2 emissions, leading to indirect environmental impacts and a financial cost. However, existing monitoring techniques can only perform a limited number of measurements throughout the night and lack spectral and spatial resolution. Therefore, satellites with improved spectral and spatial resolution are needed to enable time series analysis of light pollution trends throughout the night.
... In addition, exposure to artificial light at night (light pollution) is associated with suppression of melatonin production and desynchronization of the circadian body clock. Light desynchronization is considered a risk factor for the development of many diseases, in particular, obesity [43,46,47], metabolic syndrome/diabetes [48,49], and hypertension [50]. Another interrelated factor is chronotype, which may influence daily blood pressure dynamics and the risk of hypertension [51,52]. ...
Purpose:
The circumpolar habitat stands as one of the most vulnerable environments for human activity and health. The primary study objective was to compare sleep-related factors, light exposure, social cues, and potential confounding variables among schoolchildren residing in the European Arctic region from two settlements situated below and above the Polar Circle using validated self-reported questionnaires.
Materials and methods:
We recruited 94 children aged 13-15 years (40.4% males), matched by sex and age, from public educational institutions in two circumpolar settlements located below (Kem', Republic of Karelia; 64.6 NL) and above the Polar Circle (Apatity, Murmansk Region; 67.3 NL). Participants completed several surveys, including the Pediatric Daytime Sleepiness Scale, the Insomnia Severity Index, the Adolescent Sleep Hygiene Scale, and the Munich ChronoType Questionnaire, to evaluate sleep parameters and chronotype. The χ2 test was used to test for differences between proportions. Linear regression and multiple regression models with co-factors were applied to assess the relationship between studied indicators.
Results:
A noteworthy increase in physical activity was observed in children residing in Kem' compared to those in Apatity. Children from Apatity showed higher alcohol consumption than their counterparts from Kem'. The overall rate of excessive daytime sleepiness in the sample was 17.1%. Moderate insomnia symptoms were reported in 18.4% of adolescents living in Kem' and in 25% of respondents living in Apatity, respectively. Notably, participants from Kem' attained higher academic scores and had longer exposure to sunlight on schooldays. On the other hand, children from Apatity tended to have later bedtimes and sleep-onset times on schooldays. According to the Munich ChronoType Questionnaire data, a reliance on alarm clocks on schooldays, and a higher Sleep Stability Factor based on the Adolescent Sleep Hygiene Scale.
Discussion:
Our study indicating that higher physical activity and longer sunlight exposure among Kem' children on schooldays are associated with earlier wake-up times during schooldays, earlier bedtime whole week, reduced dependence on alarm clocks, and higher academic achievements. The results of older schoolchildren differ from many works published previously in the USA, Argentina, and Japan, which could be explained by the season when the study was performed. Here, we observed a negative impact on school performance and sleep parameters in children living in high latitudes, namely in circumpolar regions.
Conclusions:
Our study points out that adolescents living above the Polar Circle tend to have sleep problems, e.g., late sleep-onset times, higher excessive daytime sleepiness, and insomnia-related symptoms, because of experiencing reduced exposure to natural light. Future research encompassing assessments across all four seasons will provide a more comprehensive understanding.
... Light at night has been shown to modify food intake in vertebrates, but also to cause various metabolic disorders (e.g. weight gain, lipid accumulation in the liver, impaired glucose tolerance; Batra et al., 2019;Fleury et al., 2020;Fonken et al., 2010;Masís-Vargas et al., 2019). Even though we did not detect a negative effect of ALAN on the life span of V. canescens in our study, changes in the timing of feeding and potential metabolism alterations due to light at night may affect fitness, and more specifically reproductive traits (Xu et al., 2011). ...
The increasing use of artificial light at night (ALAN) is an anthropogenic disturbance with eco-evolutionary consequences for both nocturnal and diurnal organisms. It has been hypothesized that light pollution could create a 'night-light' niche providing new opportunities for diurnal organisms to forage and reproduce at night, with fitness consequences still scarcely explored. We exposed diurnal parasitoid wasps (Venturia canescens) to control (0 lx), low (0.7 lx) or high (20 lx) intensity of light at night throughout their lives and monitored changes in behavioural and life history traits. Light pollution influenced the night-time activity of wasps, with increased feeding and egg laying at night and a tendency for higher night-time reproductive success under a high intensity of light pollution. Surprisingly, high light pollution also increased the wasps' life span. Light pollution did not significantly affect lifetime reproductive success but did affect the distribution of ovipositions between day and night. Additionally, we showed that reproductive senescence occurred in V. canescens and that offspring development time was influenced by light pollution, in interaction with maternal age. These findings highlight the use of the 'night-light' niche in a diurnal insect exposed to light pollution, with potential implications for population dynamics, especially in natural conditions.
... A high-fat diet only induces obesity in mice if given ad libitum, but not only during the active phase [10]. Light at night increases body weight gain and the risk of glucose intolerance in mice fed with normal chow [11]. Glucose-induced insulin release is reduced in islet cells lacking the clock gene Bmal1, and these mice exhibit glucose intolerance [12]. ...
Circadian rhythm disruption is associated with impaired glucose homeostasis and type 2 diabetes. For example, night shift work is associated with an increased risk of gestational diabetes. However, the effects of chronic circadian disruption since early life on adult metabolic health trajectory remain unknown. Here, using the “Short Day” (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was used to disrupt mouse circadian rhythms across the lifespan, we investigated glucose homeostasis in adult mice. Adult SD mice were fully entrained into the 8 h/8 h LD cycle, and control mice were entrained into the 12 h/12 h LD cycle. Under a normal chow diet, female and male SD mice displayed a normal body weight trajectory. However, female but not male SD mice under a normal chow diet displayed glucose intolerance and insulin resistance, which are associated with impaired insulin signaling/AKT in the skeletal muscle and liver. Under high-fat diet (HFD) challenges, male but not female SD mice demonstrated increased body weight gain compared to controls. Both male and female SD mice developed glucose intolerance under HFD. Taken together, these results demonstrate that environmental disruption of circadian rhythms contributes to obesity in a sexually dimorphic manner but increases the risk of glucose intolerance and insulin resistance in both males and females.
... In their natural habitat, diurnal and nocturnal animals experience light at different times of the temporal day, and also at different intensities, and can therefore have different responses to light at night. Diurnal animals can extend their active time into the night, thereby disrupting their sleep patterns (Aschoff 1960;Fonken et al. 2010;Russart and Nelson 2018). In contrast, the activity of nocturnal animals may be suppressed (Aschoff 1960;Viljoen and Oosthuizen 2023;Zhang et al. 2020). ...
Urbanization, and the accompanying artificial light at night (ALAN), can disrupt the activity of animals. Such disruptions at the base of a food web can ripple through the ecosystem. Most studies of ALAN are performed in the laboratory. Thus, we lack basic information about the circadian responses of animals under natural environmental conditions to fully evaluate the impact of ALAN. We studied the behaviour and activity of wild-caught, peri-urban single-striped grass mice (Lemniscomys rosalia) under a natural treatment and in a standard laboratory treatment, including dim light at night to mimic conditions that they could experience. The species exhibited predominantly
crepuscular activity under all experimental treatments. It showed the highest level of
activity under the natural treatment, whereas ALAN significantly suppressed its activity. Males were more active than females under all experimental treatments. The marked changes in activity under ALAN is of particular concern since global change in combination with urbanization can lead to a change in vegetation density and composition that will decrease the number of suitable microhabitats and expose small mammals to novel habitat changes. We suggest that the single-striped mice could become vulnerable because of urbanization, leading to impacts on its ecosystem
broadly.
... Genetic ablation of CGs including PER2, CLOCK, and/or BMAL1, led to increased food intake during rest time, decreased circadian behavior, impaired insulin action, and increased serum levels of triglycerides, cholesterol and glucose, which lead to obesity and metabolic syndrome in mice(Shi et al., 2013;Turek et al., 2005). Artificial light exposure at night induced elevated food intake during the normal rest period, leading to increased body mass and decreased glucose tolerance in mice(Fonken et al., 2010). Time-delayed eating behavior caused glucose intolerance and irregular lipid metabolism, which contributed to occurrence of obesity and lipid disorders in mice(Wu et al., 2015). ...
The circadian clock is an endogenous biochemical timing system that coordinates the physiology and behavior of organisms to earth's ∼24-hour circadian day/night cycle. The central circadian clock synchronized by environmental cues hierarchically entrains peripheral clocks throughout the body. The circadian system modulates a wide variety of metabolic signaling pathways to maintain whole-body metabolic homeostasis in mammals under changing environmental conditions. Endocrine fibroblast growth factors (FGFs), namely FGF15/19, FGF21, and FGF23, play an important role in regulating systemic metabolism of bile acids, lipids, glucose, proteins, and minerals. Recent evidence indicates that endocrine FGFs function as nutrient sensors that mediate multifactorial interactions between peripheral clocks and energy homeostasis by regulating the expression of metabolic enzymes and hormones. Circadian disruption induced by environmental stressors or genetic ablation is associated with metabolic dysfunction and diurnal disturbances in FGF signaling pathways that contribute to the pathogenesis of metabolic diseases. Time-restricted feeding strengthens the circadian pattern of metabolic signals to improve metabolic health and prevent against metabolic diseases. Chronotherapy, the strategic timing of medication administration to maximize beneficial effects and minimize toxic effects, can provide novel insights into linking biologic rhythms to drug metabolism and toxicity within the therapeutical regimens of diseases. Here we review the circadian regulation of endocrine FGF signaling in whole-body metabolism and the potential effect of circadian dysfunction on the pathogenesis and development of metabolic diseases. We also discuss the potential of chrononutrition and chronotherapy for informing the development of timing interventions with endocrine FGFs to optimize whole-body metabolism in humans. SIGNIFICANCE STATEMENT: The circadian timing system governs physiological, metabolic, and behavioral functions in living organisms. The endocrine fibroblast growth factor (FGF) family (FGF15/19, FGF21, and FGF23) plays an important role in regulating energy and mineral metabolism. Endocrine FGFs function as nutrient sensors that mediate multifactorial interactions between circadian clocks and metabolic homeostasis. Chronic disruption of circadian rhythms increases the risk of metabolic diseases. Chronological interventions such as chrononutrition and chronotherapy provide insights into linking biological rhythms to disease prevention and treatment.
Aberrant light/dark (LD) cycles are prevalent in modern society due to electric light usage, leading to mood disorders from circadian disruption or misalignment. However, research on the physiological and behavioral effects of LD variations on brain neurotransmitters is limited. We investigated the effects of extreme LD cycles on body weight (BW), core body temperature (Tcore), locomotor activity (ACT), emotional behaviors, and monoamine levels (noradrenaline [NA], dopamine [DA], and serotonin [5-HT]) in male Wistar rats that were exposed to 1 month of either long light phase (20 L:4D), long dark phase (4 L:20D), or normal (12 L:12D) LD cycles. The 20 L:4D rats exhibited blunted rhythms, with decreased amplitude and advanced/delayed acrophase in Tcore and ACT, alongside increased BW. The 4 L:20D rats showed circadian misalignment, with increased/decreased amplitude in Tcore or ACT and delayed acrophase in Tcore and ACT, also gaining BW. In the 20 L:4D group, NA and 5-HT levels decreased in the suprachiasmatic nucleus and amygdala, respectively, while the 4 L:20D group had increased DA and 5-HT levels in the caudate putamen and dorsomedial hypothalamus, respectively. Open field and social interaction tests indicated anxiety-like behaviors in both test groups. Overall, each extreme LD cycle affected Tcore, ACT amplitude, acrophase, and monoamine levels differently, inducing anxiogenic responses.
Variations in day length, or photoperiodism, whether natural or artificial light, significantly impact biological, physiological, and behavioral processes within the brain. Both natural and artificial light sources are environmental factors that significantly influence brain functions and mental well-being. Photoperiodism is a phenomenon, occurring either over a 24 h cycle or seasonally and denotes all biological responses of humans and animals to these fluctuations in day and night length. Conversely, artificial light occurrence refers to the presence of light during nighttime hours and/or its absence during the daytime (unnaturally long and short days, respectively). Light at night, which is a form of light pollution, is prevalent in many societies, especially common in certain emergency occupations. Moreover, individuals with certain mental disorders, such as depression, often exhibit a preference for darkness over daytime light. Nevertheless, disturbances in light patterns can have negative consequences, impacting brain performance through similar mechanisms albeit with varying degrees of severity. Furthermore, changes in day length lead to alterations in the activity of receptors, proteins, ion channels, and molecular signaling pathways, all of which can impact brain health. This review aims to summarize the mechanisms by which day length influences brain functions through neural circuits, hormonal systems, neurochemical processes, cellular activity, and even molecular signaling pathways.
The circadian system, which controls a variety of rhythms in our bodies, is under a lot of stress in modern times. With the demand for products and services expanding throughout the day, rapid industrialisation and globalisation of the economy, and nontraditional work schedules are becoming increasingly prevalent. Employees who work shifts that involve the night must stay awake when their biological clocks signal inactivity. A growing body of research suggests that shift work raises the risk of several major physiological and psychological conditions, including cardiovascular disease, metabolic syndrome, obesity, immunological dysfunction, cancer, and problems during pregnancy. Due to survivorship bias and self-selection, epidemiological studies may understate shift employment’s negative effects on health.
The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronize them with daily cycles. While the central clock in the suprachiasmatic nucleus (SCN) is mainly synchronized by the light/dark cycles, the peripheral clocks react to other stimuli, including the feeding/fasting state, nutrients, sleep–wake cycles, and physical activity. During the disruption of circadian rhythms due to genetic mutations or social and occupational obligations, incorrect arrangement between the internal clock system and environmental rhythms leads to the development of obesity. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition leads to uncoupling of the peripheral clocks from the central pacemaker and to the development of metabolic disorders. The strong coupling of the SCN to the light–dark cycle creates a situation of misalignment when food is ingested during the “wrong” time of day. Food-anticipatory activity is mediated by a self-sustained circadian timing, and its principal component is a food-entrainable oscillator. Modifying the time of feeding alone greatly affects body weight, whereas ketogenic diet (KD) influences circadian biology, through the modulation of clock gene expression. Night-eating behavior is one of the causes of circadian disruption, and night eaters have compulsive and uncontrolled eating with severe obesity. By contrast, time-restricted eating (TRE) restores circadian rhythms through maintaining an appropriate daily rhythm of the eating–fasting cycle. The hypothalamus has a crucial role in the regulation of energy balance rather than food intake. While circadian locomotor output cycles kaput (CLOCK) expression levels increase with high-fat diet-induced obesity, peroxisome proliferator-activated receptor-alpha (PPARα) increases the transcriptional level of brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1 (BMAL1) in obese subjects. In this context, effective timing of chronotherapies aiming to correct SCN-driven rhythms depends on an accurate assessment of the SCN phase. In fact, in a multi-oscillator system, local rhythmicity and its disruption reflects the disruption of either local clocks or central clocks, thus imposing rhythmicity on those local tissues, whereas misalignment of peripheral oscillators is due to exosome-based intercellular communication.
Consequently, disruption of clock genes results in dyslipidemia, insulin resistance, and obesity, while light exposure during the daytime, food intake during the daytime, and sleeping during the biological night promote circadian alignment between the central and peripheral clocks. Thus, shift work is associated with an increased risk of obesity, diabetes, and cardiovascular diseases because of unusual eating times as well as unusual light exposure and disruption of the circadian rhythm.
A Cosmic Mind emanating subatomic living cosmic evolutionary intelligence agents called microvita may become the scientifically required explanation for the rapid origin of new, immediately viable species from existing species during climate crises, as well as for forming the first viruses utilized in the origin of protoplasmic life. According to Prabhat Ranjan Sarkar, microvita are emanated by the Cosmic Mind to implement Cosmic desires. With Cosmic approval, microvita may create new and immediately viable species by directing transposons or “jumping genes” in an organism’s genome to transfer and multiply a specific portion of the genome’s shiftable DNA to pre-planned DNA sites in the genome. These rearranged and possibly expanded genomes will generate from current species members a pre-planned new species, pre-adapted to live and thrive in a different environment or ecological niche during periods of catastrophic climate change. The new species requires no further adaptations to the changed environment by Darwinian natural selection, except for minor adaptations that may occur due to the normal genetic variability within a species population. Divine selection, implemented by microvita-directed transposons, regularly creates viable new species that natural selection, based only on the laws of physics and chemistry, could almost never create from existing species.
The circadian clock system, an evolutionarily conserved mechanism, orchestrates diurnal rhythms in biological activities such as behavior and metabolism, aligning them with the earth's 24-hour light/dark cycle. This synchronization enables organisms to anticipate and adapt to predictable environmental changes, including nutrient availability. However, modern lifestyles characterized by irregular eating and sleeping habits disrupt this synchrony, leading to metabolic disorders such as obesity and metabolic syndrome, evidenced by higher obesity rates among shift workers. Conversely, circadian disturbances are also associated with reduced nutrient absorption and an increased risk of malnutrition in populations such as the critically ill or the elderly. The precise mechanisms of these disturbances in leading to either overnutrition or undernutrition is complex and not yet fully understood. Glucose, a crucial energy source, is closely linked to obesity when consumed excessively and to weight loss when intake is reduced, which suggests that circadian regulation of glucose metabolism is a key factor connecting circadian disturbances with nutritional outcomes. In this review, we describe how the biological clock in various tissues regulates glucose metabolism, with a primary focus on studies utilizing animal models. Additionally, we highlight current clinical evidence supporting the association between circadian disturbance and glucose metabolism, arguing that such disruption could predominantly contribute to undernutrition due to impaired efficient utilization of nutrients.
Background
Light at night disrupts circadian rhythms, and circadian disruption is a risk factor for type 2 diabetes. Whether personal light exposure predicts diabetes risk has not been demonstrated in a large prospective cohort. We therefore assessed whether personal light exposure patterns predicted risk of incident type 2 diabetes in UK Biobank participants, using ∼13 million hours of light sensor data.
Methods
Participants (N = 84,790, age (M ± SD) = 62.3 ± 7.9 years, 58% female) wore light sensors for one week, recording day and night light exposure. Circadian amplitude and phase were modeled from weekly light data. Incident type 2 diabetes was recorded (1997 cases; 7.9 ± 1.2 years follow-up; excluding diabetes cases prior to light-tracking). Risk of incident type 2 diabetes was assessed as a function of day and night light, circadian phase, and circadian amplitude, adjusting for age, sex, ethnicity, socioeconomic and lifestyle factors, and polygenic risk.
Findings
Compared to people with dark nights (0–50th percentiles), diabetes risk was incrementally higher across brighter night light exposure percentiles (50–70th: multivariable-adjusted HR = 1.29 [1.14–1.46]; 70–90th: 1.39 [1.24–1.57]; and 90–100th: 1.53 [1.32–1.77]). Diabetes risk was higher in people with lower modeled circadian amplitude (aHR = 1.07 [1.03–1.10] per SD), and with early or late circadian phase (aHR range: 1.06–1.26). Night light and polygenic risk independently predicted higher diabetes risk. The difference in diabetes risk between people with bright and dark nights was similar to the difference between people with low and moderate genetic risk.
Interpretation
Type 2 diabetes risk was higher in people exposed to brighter night light, and in people exposed to light patterns that may disrupt circadian rhythms. Avoidance of light at night could be a simple and cost-effective recommendation that mitigates risk of diabetes, even in those with high genetic risk.
Funding
Australian Government Research Training Program.
Artificial light at night (ALAN) is an emerging environmental pollutant that threatens public health. Recently, ALAN has been identified as a risk factor for obesity; however, the role of ALAN and its light wavelength in hepatic lipid metabolic homeostasis remains undetermined. We showed that chronic dim (~5 lx) ALAN (dLAN) exposure significantly promoted hepatic lipid accumulation in obese or diabetic mice, with the most severe effect of blue light and little effect of green or red light. These metabolic phenotypes were attributed to blue rather than green or red dLAN interfering with hepatic lipid metabolism, especially lipogenesis and lipolysis. Further studies found that blue dLAN disrupted hepatic lipogenesis and lipolysis processes by inhibiting hepatic REV‐ERBs. Mechanistically, feeding behavior mediated the regulation of dLAN on hepatic REV‐ERBs. In addition, different effects of light wavelengths at night on liver REV‐ERBs depended on the activation of the corticosterone (CORT)/glucocorticoid receptor (GR) axis. Blue dLAN could activate the CORT/GR axis significantly while other wavelengths could not. Notably, we demonstrated that exogenous melatonin could effectively inhibit hepatic lipid accumulation and restore the hepatic GR/REV‐ERBs axis disrupted by blue dLAN. These findings demonstrate that dLAN promotes hepatic lipid accumulation in mice via a short‐wavelength‐dependent manner, and exogenous melatonin is a potential therapeutic approach. This study strengthens the relationship between ALAN and hepatic lipid metabolism and provides insights into directing ambient light.
Background
Artificial light at night, a well-recognized circadian clock disrupter, causes disturbances in endocrine homeostasis. However, the association of artificial light at night with polycystic ovary syndrome (PCOS) is still unknown. This study examines the effects of outdoor artificial light at night on sex hormones, glucose homeostasis markers, and PCOS prevalence in Anhui Province, China.
Methods
We recruited 20633 women of reproductive age from Anhui Medical University Reproductive Medicine Center. PCOS was diagnosed according to Rotterdam criteria. We estimated long-term (previous year) and short-term (previous month) artificial light at night values for residential addresses using 500-meter resolution satellite imagery. We fitted multivariable models, using both linear and logistic regression, to estimate the association of artificial light at night with sex hormones, glucose homeostasis markers, and PCOS prevalence.
Results
Both long-term and short-term exposure to outdoor artificial light at night were negatively associated with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, while positively associated with testosterone, fasting insulin, HOMA-IR, and HOMA-β levels. The second-highest quintile of artificial light at night was associated with increased PCOS prevalence (OR long-term =1.4, 95% CI: 1.2,1.6); OR short-term =1.3, 95% CI: 1.1,1.5) compared to the lowest quintile. In addition, prevalence of PCOS was linearly associated with long-term exposure to artificial light at night, but non-linearly associated with short-term exposure. This association was more evident in younger, obese or overweight, moderately educated, rural women, and for the summer and fall seasons.
Conclusions
Outdoor artificial light at night may be a novel risk factor for PCOS.
Scope
Diet and exercise are significant players in obesity and metabolic diseases. Time‐restricted feeding (tRF) has been shown to improve metabolic responses by regulating circadian clocks but whether it acts synergically with exercise remains unknown. It is hypothesized that forced exercise alone or combined with tRF alleviates obesity and its metabolic complications.
Methods and results
Male C57bl6 mice are fed with high‐fat or a control diet for 12 weeks either ad libitum or tRF for 10 h during their active period. High‐fat diet (HFD)‐fed mice are divided into exercise (treadmill for 1 h at 12 m min ⁻¹ alternate days for 9 weeks and 16 m min ⁻¹ daily for the following 3 weeks) and non‐exercise groups. tRF and tRF‐Ex significantly decreased body weight, food intake, and plasma lipids, and improved glucose tolerance. However, exercise reduced only body weight and plasma lipids. tRF and tRF‐Ex significantly downregulated Fasn, Hmgcr , and Srebp1c , while exercise only Hmgcr . HFD feeding disrupted clock genes, but exercise, tRF, and tRF‐Ex coordinated the circadian clock genes Bmal1, Per2 , and Rev‐Erbα in the liver, adipose tissue, and skeletal muscles.
Conclusion
HFD feeding disrupted clock genes in the peripheral organs while exercise, tRF, and their combination restored clock genes and improved metabolic consequences induced by high‐fat diet feeding.
Light is an environmental factor that is extrinsic to animals themselves and that exerts a profound influence on the regulation of circadian, neurohormonal, metabolic, and neurobehavioral systems of all animals, including research animals. These widespread biologic effects of light are mediated by distinct photoreceptors—rods and cones that comprise the conventional visual system and melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) of the nonvisual system that interact with the rods and cones. The rods and cones of the visual system, along with the ipRGCs of the nonvisual system, are species distinct in terms of opsins and opsin concentrations and interact with one another to provide vision and regulate circadian rhythms of neurohormonal and neurobehavioral responses to light. Here, we review a brief history of lighting technologies, the nature of light and circadian rhythms, our present understanding of mammalian photoreception, and current industry practices and standards. We also consider the implications of light for vivarium measurement, production, and technological application and provide simple recommendations on artificial lighting for use by regulatory authorities, lighting manufacturers, designers, engineers, researchers, and research animal care staff that ensure best practices for optimizing animal health and well-being and, ultimately, improving scientific outcomes.
Photobiomodulation therapy (PBMT), formerly known as low-level laser therapy, is the targeted application of light for therapeutic purposes at a low level below that associated with damage to structural proteins. This may be a laser or a broader spectrum light source such as a light-emitting diode (LED), which may selectively achieve changes in subcellular, local, regional and centrally mediated systemic processes associated with healing, repair and the regeneration of tissues [1, 2]. In addition to the potential benefits of the promotion of an increase in cellular numbers by mitosis and a corresponding increase in the production of important matrix materials such as collagen and bone along with an enhanced vasculature, there can also be seen resolution of inflammation and the mitigation, up to inhibition of pain [3, 4]. Furthermore, therapeutic photonic conditioning of tissues as a prequel or synchronous to exposure to a noxious stimulus such as chemotherapy or radiotherapy can increase cellular stress resistance against apoptosis [5, 6]. Given the very wide range of possible applications, PBMT has excited considerable interest across a multitude of possible applications, as an adjunct to augment the normal procedures in clinical dentistry [7, 8]. Following over 50 years of research at the level of cellular, animal and more recently human clinical trials, there is a considerable published evidence base. To date the broader integration of this approach as a tool to assist the dental team to optimise a clinical intervention has been slow to be adopted. Given the extent of the current knowledge base which is rapidly expanding due to the heightened awareness of the potential value of this approach to enhanced healing and tissue management, it is inevitable that PBMT will in time become a standard evidence-based procedure in daily clinical practice. In this chapter we provide a contemporary overview of this important subject with a particular view to help guide the clinician with an interest in learning the processes involved to safely and successfully explore the potential merits of this approach to patient care.
Glucose metabolism is impacted by circadian disruption. Dinner-bedtime interval (DBI) was an accessible indicator to reflect the alignment between dinner time and circadian clock. We aimed to investigate the association of DBI with type 2 diabetes mellitus (T2DM).
7676 adult subjects from the Henan Rural Cohort were included. Their demographic information including dinner time and bedtime was collected. Fasting venous blood samples were collected for biochemical determinations. Generalized linear regression model was used to analyze the factors influencing DBI. Furthermore, logistic regression incorporated with restricted cubic spline model was applied to evaluate the association between DBI and T2DM.
The results of multiple linear regression model showed that age (β: -0.018, 95% CI: -0.021, -0.015) was negatively correlated with DBI. Female (β: 0.311, 95% CI: 0.229, 0.393), junior high school education (β: 0.246, 95% CI: 0.187, 0.306), high school education or above (β: 0.346, 95% CI: 0.259, 0.433), average monthly income with 1000–1999 CNY(0.102, 95% CI: 0.032, 0.171), average monthly income ≥ 2000 CNY (β: 0.164, 95% CI: 0.076, 0.251), moderate physical activity (β: 0.134, 95% CI: 0.071, 0.197), current smokers (β: 0.214, 95% CI: 0.118, 0.309), current drinkers (β: 0.099, 95% CI: 0.008, 0.190) were positively correlated with DBI. Furthermore, DBI was significantly associated with T2DM (adjusted OR: 0.910, 95%CI: 0.845–0.979, P = 0.012). DBI longer than 3 h was associated with decreased risk of T2DM (adjusted OR: 0.773, 95%CI: 0.648–0.921, P = 0.004).
DBI larger than 3 h is beneficial to T2DM prevention. Further investigation is required to verify the association.
Melatonin is synthesized rhythmically under control of circadian oscillators by the retinas of non-mammalian vertebrates. Here we report that the retinas of some strains of laboratory mice exhibit robust circadian rhythms of melatonin synthesis which can be entrained by light in vitro. The rd mutation results in progressive loss of the rod and later cone photoreceptors. In mice homozygous for rd retinal melatonin synthesis is rhythmic at postnatal day 28 but not in older animals. Apparently rod photoreceptors are necessary for the expression of the circadian rhythm of melatonin synthesis but not for the synthesis itself. The many genetic and molecular tools available in the mouse can now be applied to analysis of the retinal circadian oscillator.
Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since the period of this oscillation is of approximately 24 h, to keep synchrony with the environment, circadian rhythms need to be entrained daily by means of Zeitgeber ("time giver") signals, such as the light-dark cycle. Recent advances in the neurophysiology and molecular biology of circadian rhythmicity allow a better understanding of synchronization. In this review we cover several aspects of the mechanisms for photic entrainment of mammalian circadian rhythms, including retinal sensitivity to light by means of novel photopigments as well as circadian variations in the retina that contribute to the regulation of retinal physiology. Downstream from the retina, we examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction with SCN receptors and the resulting signal transduction pathways in suprachiasmatic neurons, as well as putative neuron-glia interactions. Finally, we describe and analyze clock gene expression and its importance in entrainment mechanisms, as well as circadian disorders or retinal diseases related to entrainment deficits, including experimental and clinical treatments.
The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night. During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis, and although rhythmic control of insulin release is recognized to be dysregulated in humans with diabetes, it is not known how the circadian clock may affect this process. Here we show that pancreatic islets possess self-sustained circadian gene and protein oscillations of the transcription factors CLOCK and BMAL1. The phase of oscillation of islet genes involved in growth, glucose metabolism and insulin signalling is delayed in circadian mutant mice, and both Clock and Bmal1 (also called Arntl) mutants show impaired glucose tolerance, reduced insulin secretion and defects in size and proliferation of pancreatic islets that worsen with age. Clock disruption leads to transcriptome-wide alterations in the expression of islet genes involved in growth, survival and synaptic vesicle assembly. Notably, conditional ablation of the pancreatic clock causes diabetes mellitus due to defective beta-cell function at the very latest stage of stimulus-secretion coupling. These results demonstrate a role for the beta-cell clock in coordinating insulin secretion with the sleep-wake cycle, and reveal that ablation of the pancreatic clock can trigger the onset of diabetes mellitus.
Shift work or night work is associated with hypertension, metabolic syndrome, cancer, and other diseases. The cause for these pathologies is proposed to be the dissociation between the temporal signals from the biological clock and the sleep/activity schedule of the night worker. We investigated the mechanisms promoting metabolic desynchrony in a model for night work in rats, based on daily 8-h activity schedules during the resting phase. We demonstrate that the major alterations leading to internal desynchrony induced by this working protocol, flattened glucose and locomotor rhythms and the development of abdominal obesity, were caused by food intake during the rest phase. Shifting food intake to the normal activity phase prevented body weight increase and reverted metabolic and rhythmic disturbances of the shift work animals to control ranges. These observations demonstrate that feeding habits may prevent or induce internal desynchrony and obesity.
Although the human genome has remained unchanged over the last 10,000 years, our lifestyle has become progressively more divergent from those of our ancient ancestors. This maladaptive change became apparent with the Industrial Revolution and has been accelerating in recent decades. Socially, we are people of the 21st century, but genetically we remain similar to our early ancestors. In conjunction with this discordance between our ancient, genetically-determined biology and the nutritional, cultural and activity patterns in contemporary Western populations, many diseases have emerged. Only a century ago infectious disease was a major cause of mortality, whereas today non-infectious chronic diseases are the greatest cause of death in the world. Epidemics of metabolic diseases (e.g., cardiovascular diseases, type 2 diabetes, obesity, metabolic syndrome and certain cancers) have become major contributors to the burden of poor health and they are presently emerging or accelerating, in most developing countries. One major lifestyle consequence is light at night and subsequent disrupted circadian rhythms commonly referred to as circadian disruption or chronodisruption. Mounting evidence reveals that particularly melatonin rhythmicity has crucial roles in a variety of metabolic functions as an anti-oxidant, anti-inflammatory chronobiotic and possibly as an epigenetic regulator. This paper provides a brief outline about metabolic dysregulation in conjunction with a disrupted melatonin rhythm.
Studies of body weight regulation have focused almost entirely on caloric intake and energy expenditure. However, a number of recent studies in animals linking energy regulation and the circadian clock at the molecular, physiological, and behavioral levels raise the possibility that the timing of food intake itself may play a significant role in weight gain. The present study focused on the role of the circadian phase of food consumption in weight gain. We provide evidence that nocturnal mice fed a high-fat diet only during the 12-h light phase gain significantly more weight than mice fed only during the 12-h dark phase. A better understanding of the role of the circadian system for weight gain could have important implications for developing new therapeutic strategies for combating the obesity epidemic facing the human population today.
Circadian rhythms govern a wide variety of physiological and metabolic functions in most organisms. At the heart of these regulatory pathways in mammals is the clock machinery, a remarkably coordinated transcription-translation system that relies on dynamic changes in chromatin states. Recent findings indicate that regulation also goes the other way, as specific elements of the clock can sense changes in cellular metabolism. Understanding in full detail the intimate links between cellular metabolism and the circadian clock machinery will provide not only crucial insights into system physiology but also new avenues toward pharmacological intervention of metabolic disorders.
There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h "day." Subjects ate 4 isocaloric meals each 28-h "day." For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling approximately 1,000 assays/subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept approximately 12 h out of phase from their habitual times, systematically decreased leptin (-17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (-20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work.
Fuller et al. (Reports, 23 May 2008, p. 1074) reported that the dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food-entrained circadian rhythms. We report that mice bearing a null mutation of Bmal1 exhibit normal food-anticipatory circadian rhythms. Lack of food anticipation in Bmal1-/- mice reported by Fuller et al. may reflect morbidity due to weight loss, thus raising questions about their conclusions.
Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results suggest that appropriate melatonin supplementation may potentially provide prophylaxis or therapy for some prominent pathologies associated with aging.
The obesity epidemic shows no signs of abating. There is an urgent need to push back against the environmental forces that are producing gradual weight gain in the population. Using data from national surveys, we estimate that affecting energy balance by 100 kilocalories per day (by a combination of reductions in energy intake and increases in physical activity) could prevent weight gain in most of the population. This can be achieved by small changes in behavior, such as 15 minutes per day of walking or eating a few less bites at each meal. Having a specific behavioral target for the prevention of weight gain may be key to arresting the obesity epidemic.
Glucocorticoids have a major effect on food intake that is underappreciated, although the effects of glucocorticoids on metabolism and abdominal obesity are quite well understood. Physiologically appropriate concentrations of naturally secreted corticosteroids (cortisol in humans, corticosterone in rats) have major stimulatory effects on caloric intake and, in the presence of insulin, preference. We first address the close relationship between glucocorticoids and energy balance under both normal and abnormal conditions. Because excess caloric intake is stored in different fat depots, we also address the systemic effects of glucocorticoids on redistribution of stored energy preponderantly into intraabdominal fat depots. We provide strong evidence that glucocorticoids modify feeding and then discuss the role of insulin on the choice of ingested calories, as well as suggesting some central neural pathways that may be involved in these actions of glucocorticoids and insulin. Finally, we discuss the evolutionary utility of these actions of the stress hormones, and how dysregulatory effects of chronically elevated glucocorticoids may occur in our modern, rich societies.
Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3) and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished by deletion of Bmal1 and is depressed in Clock mutants, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycaemia is retained. Furthermore, a high-fat diet modulates carbohydrate metabolism by amplifying circadian variation in glucose tolerance and insulin sensitivity, and mutation of Clock restores the chow-fed phenotype. Bmal1 and Clock, genes that function in the core molecular clock, exert profound control over recovery from insulin-induced hypoglycaemia. Furthermore, asynchronous dietary cues may modify glucose homeostasis via their interactions with peripheral molecular clocks.
The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia, and hypoinsulinemia. Expression of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice. These results suggest that the circadian clock gene network plays an important role in mammalian energy balance.
The discovery of an internal temporal clockwork that coordinates behavior and metabolism according to the rising and setting of the sun was first revealed in flies and plants. However, in the past decade, a molecular transcription-translation feedback loop with similar properties has also been identified in mammals. In mammals, this transcriptional oscillator programs 24-hour cycles in sleep, activity and feeding within the master pacemaker neurons of the suprachiasmatic nucleus of the hypothalamus. More recent studies have shown that the core transcription mechanism is also present in other locations within the brain, in addition to many peripheral tissues. Processes ranging from glucose transport to gluconeogenesis, lipolysis, adipogenesis and mitochondrial oxidative phosphorylation are controlled through overlapping transcription networks that are tied to the clock and are thus time sensitive. Because disruption of tissue timing occurs when food intake, activity and sleep are altered, understanding how these many tissue clocks are synchronized to tick at the same time each day, and determining how each tissue 'senses time' set by these molecular clocks might open new insight into human disease, including disorders of sleep, circadian disruption, diabetes and obesity.
Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin - failure to control blood glucose levels results. Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.
In this review, we present evidence from human and animal studies to evaluate the hypothesis that sleep and circadian rhythms have direct impacts on energy metabolism, and represent important mechanisms underlying the major health epidemics of obesity and diabetes. The first part of this review will focus on studies that support the idea that sleep loss and obesity are "interacting epidemics." The second part will discuss recent evidence that the circadian clock system plays a fundamental role in energy metabolism at both the behavioral and molecular levels. These lines of research must be seen as in their infancy, but nevertheless, have provided a conceptual and experimental framework that potentially has great importance for understanding metabolic health and disease.
The circadian clock programs daily rhythms and coordinates multiple behavioral and physiological processes, including activity, sleep, feeding, and fuel homeostasis. Recent studies indicate that genetic alteration in the core molecular clock machinery can have pronounced effects on both peripheral and central metabolic regulatory signals. Many metabolic systems also cycle and may in turn affect function of clock genes and circadian systems. However, little is known about how alterations in energy balance affect the clock. Here we show that a high-fat diet in mice leads to changes in the period of the locomotor activity rhythm and alterations in the expression and cycling of canonical circadian clock genes, nuclear receptors that regulate clock transcription factors, and clock-controlled genes involved in fuel utilization in the hypothalamus, liver, and adipose tissue. These results indicate that consumption of a high-calorie diet alters the function of the mammalian circadian clock.
The circadian pacemaker in the suprachiasmatic nuclei (SCN) controls endogenous near 24-h physiological and behavioral rhythms in metabolism, neuroendocrine function, and locomotor activity. Recently, we showed that vasoactive intestinal polypeptide (VIP) and its receptor, VPAC(2) are critical to the intercellular communication between individual SCN neurons, and appropriate synchronization and phasing of these oscillatory cells. Mice defective in VIP signaling manifest grossly impaired circadian rhythms of SCN neuronal firing activity and are typically unable to maintain rhythmic wheel-running behavior in the absence of external time cues. Here we report that daily rhythms of metabolism and feeding behavior are also overtly altered in these animals. Under diurnal conditions (12:12-h light-dark; LD), metabolic and feeding rhythms are advanced in mice lacking either VIP or VPAC(2) receptor expression, peaking in the late day, rather than early night, as observed in wild-type mice. When placed in constant light (LL), both VIP-deficient and VPAC(2) receptor-knockout mice exhibit dampening of metabolic and feeding rhythms, which deteriorate after a few days. In addition, overall metabolic rate is greatly reduced in VPAC(2)-knockout mice, when compared with wild-type mice, regardless of lighting condition. The advancement of metabolic and feeding rhythms in these mice under LD suggests that these rhythms are less sensitive to masking by light. These results demonstrate that altering SCN function not only affects neuronal and wheel-running activity rhythms but also dramatically impairs temporal regulation of metabolism and feeding.
When food is plentiful, circadian rhythms of animals are powerfully entrained by the light-dark cycle. However, if animals have access to food only during their normal sleep cycle, they will shift most of their circadian rhythms to match the food availability. We studied the basis for entrainment of circadian rhythms by food and light in mice with targeted disruption of the clock gene Bmal1, which lack circadian rhythmicity. Injection of a viral vector containing the Bmal1 gene into the suprachiasmatic nuclei of the hypothalamus restored light-entrainable, but not food-entrainable, circadian rhythms. In contrast, restoration of the Bmal1 gene only in the dorsomedial hypothalamic nucleus restored the ability of animals to entrain to food but not to light. These results demonstrate that the dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food entrainment of circadian rhythms.
Following blinding there is a rapid and sustained increase in eating and drinking during the light portion of a light-dark (L-D) cycle. Group nocturnal rhythms in eating and drinking are retained in attenuated form for at least 10 days; sixty days after blinding these rhythms are absent. For sighted rats the food/water ratio is three times greater during the light than during the dark; this difference is greatly reduced almost immediately after blinding. Continuous illumination almost immediately suppresses water intake and abolishes group nocturnal rhythms in eating and drinking within 9–11 days. Nocturnal eating and drinking rhythms re-entrain within 7–9 days following an inversion of the L-D cycle. Animals blinded between 12 and 36 hr after such an inversion remain residually entrained to the original L-D cycle for at least 1 month, but animals blinded at 48–120 hr re-entrain to the new cycle. These differences persist for surprisingly long times and suggest that the initial period following a change in environmental illumination is most critical for re-entrainment of eating and drinking which may then proceed relatively normally in the absence of further visual stimulation. Nocturnal patterns of drinking are present in essentially adult form in rats 23 days old; blinding on Day 14 but not on Day 18 or later prevents the appearance of these rhythms. The early perinatal period is not critical for entrainment of eating and drinking rhythms since animals first exposed to alternating L-D patterns of illumination at 59 days of age display nocturnal behavior patterns shortly thereafter. The influence of daytime feeding schedules on nocturnal drinking patterns is described and the neural basis for rhythmic light-dependent behavior considered.
Increasing evidence suggests that disrupted temporal organization impairs behavior, cognition, and affect; further, disruption of circadian clock genes impairs sleep–wake cycle and social rhythms which may be implicated in mental disorders. Despite this strong evidence, a gap in understanding the neural mechanisms of this interaction obscures whether biological rhythms disturbances are the underlying causes or merely symptoms of mental disorder. Here, we review current understanding, emerging concepts, gaps, and opportunities pertinent to (1) the neurobiology of the interactions between circadian oscillators and the neural circuits subserving higher brain function and behaviors of relevance to mental health, (2) the most promising approaches to determine how biological rhythms regulate brain function and behavior under normal and pathological conditions, (3) the gaps and challenges to advancing knowledge on the link between disrupted circadian rhythms/sleep and psychiatric disorders, and (4) the novel strategies for translation of basic science discoveries in circadian biology to clinical settings to define risk, prevent or delay onset of mental illnesses, design diagnostic tools, and propose new therapeutic strategies. The review is organized around five themes pertinent to (1) the impact of molecular clocks on physiology and behavior, (2) the interactions between circadian signals and cognitive functions, (3) the interface of circadian rhythms with sleep, (4) a clinical perspective on the relationship between circadian rhythm abnormalities and affective disorders, and (5) the pre-clinical models of circadian rhythm abnormalities and mood disorders.
The bedtime of preschoolers/pupils/students in Japan has become progressively later with the result sleep duration has become progressively shorter. With these changes, more than half of the preschoolers/pupils/students in Japan recently have complained of daytime sleepiness, while approximately one quarter of junior and senior high school students in Japan reportedly suffer from insomnia. These preschoolers/pupils/students may be suffering from behaviorally induced insufficient sleep syndrome due to inadequate sleep hygiene. If this diagnosis is correct, they should be free from these complaints after obtaining sufficient sleep by avoiding inadequate sleep hygiene. However, such a therapeutic approach often fails. Although social factors are often involved in these sleep disturbances, a novel clinical notion – asynchronization – can further a deeper understanding of the pathophysiology of these disturbances. The essence of asynchronization is a disturbance in various aspects (e.g., cycle, amplitude, phase and interrelationship) of the biological rhythms that normally exhibit circadian oscillation, presumably involving decreased activity of the serotonergic system. The major trigger of asynchronization is hypothesized to be a combination of light exposure during the night and a lack of light exposure in the morning. In addition to basic principles of morning light and an avoidance of nocturnal light exposure, presumable potential therapeutic approaches for asynchronization involve both conventional ones (light therapy, medications (hypnotics, antidepressants, melatonin, vitamin B12), physical activation, chronotherapy) and alternative ones (kampo, pulse therapy, direct contact, control of the autonomic nervous system, respiration (qigong, tanden breathing), chewing, crawling). A morning-type behavioral preference is described in several of the traditional textbooks for good health. The author recommends a morning-type behavioral lifestyle as a way to reduce behavioral/emotional problems, and to lessen the likelihood of falling into asynchronization.
Rats, mice and other species can behaviorally anticipate a predictable daily mealtime by entrainment of circadian oscillators (food-entrainable oscillators) distinct from those (light-entrainable oscillators) that regulate light-dark entrained rhythms of behavior and physiology. Neurobiological analysis of food-anticipatory rhythms has progressed slowly but is gaining pace. Food-anticipatory rhythms have proven to be surprisingly robust to many neural and circadian clock gene perturbations. A few neural ablation sites or gene mutations have been associated with loss or marked attenuation of anticipatory rhythms, but in each case there are apparently conflicting reports. Attenuation of food-anticipatory rhythms following neural or genetic perturbations could result from actions upstream or downstream from the clock mechanism, and could be limited to certain behavioral endpoints or recording conditions. Failure to observe attenuation could reflect compensation by alternate timing mechanisms that do not involve food-entrainable oscillators. To facilitate progress in neurobiological analysis of food-anticipatory rhythms, criteria for distinguishing among formally distinct mechanisms by which animals might anticipate a daily meal are reviewed, and procedural variables that can affect the expression of food-anticipatory rhythms in neurobiologically intact or compromised animals are identified.
Melatonin levels, metabolic parameters, circadian rhythm activity patterns, and behavior were observed in rats subjected to a 12-h/12-h light/dark cycle (LD) compared to animals exposed to continuous dark (DD) or continuous light (LL). LD and DD animals were similar in melatonin levels, food intake, relative food intake, feed efficiency, water intake, circadian activity levels, and behavior. LL animals had lower melatonin levels in the subjective dark compared to LD and DD animals. Food intake, relative food intake, and water intake values were lower and feed efficiency was more positive in LL animals compared to LD and DD animals. In addition, LL animals exhibited greater visceral adiposity than the other two groups. The circadian rhythmicity of activity became free-running in LL animals and there was a decrease in overall activity. Notable behavioral changes in LL animals were an increase in irritability and excitability. Results indicate that a decrease in melatonin levels and concomitant changes in metabolism, circadian rhythms, and behavior are consequences of exposure to constant light.
Plasma melatonin concentrations in non-dipping patients show a blunted daily rhythm. Melatonin has a capacity to improve disturbances in biological rhythms. Hypertensive TGR(mRen2)27 (TGR) rats with an upregulated renin-angiotensin system and inverted blood pressure profile were used to elucidate whether melatonin is able to influence the control of blood pressure.
Melatonin was administered in drinking water to normotensive Sprague-Dawley (SD) and hypertensive TGR rats during the dark phase of the light: dark cycle 12: 12 for 4 weeks.
The effect of melatonin on blood pressure was monitored, and the expression of clock genes per2 and bmal1 and melatonin receptor MT1 in the suprachiasmatic nucleus (SCN) and the heart was measured by real time polymerase chain reaction during a 24-h cycle.
The administration of melatonin did not influence clock gene expression in the SCN but its effect on clock gene expression in the heart was phase dependent in both SD and TGR rats. Melatonin administration did not decrease the expression of melatonin receptors in the SCN and the heart. Melatonin did not decrease blood pressure in TGR rats but influenced the peripheral oscillator in the heart independently of the SCN. A modified function of molecular circadian oscillators in the heart can interfere with anticipation and disturb the adaptation of this organ to pressure overload.
Individuals are increasingly exposed to light at night. Exposure to constant light (LL) disrupts circadian rhythms of locomotor activity, body temperature, hormones, and the sleep-wake cycle in animals. Other behavioural responses to LL have been reported, but are inconsistent. The present experiment sought to determine whether LL produces changes in affective responses and whether behavioural changes are mediated by alterations in glucocorticoid concentrations. Relative to conspecifics maintained in a light/dark cycle (LD, 16:8 light/dark), male Swiss-Webster mice exposed to LL for three weeks increased depressive-like behavioural responses as evaluated by the forced swim test and sucrose anhedonia. Furthermore, providing a light escape tube reversed the effects of LL in the forced swim test. LL mice displayed reduced anxiety as evaluated by the open field and elevated-plus maze. Glucocorticoid concentrations were reduced in the LL group suggesting that the affective behavioural responses to LL are not the result of elevated corticosterone. Additionally, mice housed in LD with a clear tube displayed increased paired testes mass as compared to LL mice. Taken together, these data provide evidence that exposure to unnatural lighting can induce significant changes in affect, increasing depressive-like and decreasing anxiety-like responses.
The circadian clock controls energy homeostasis by regulating circadian expression and/or activity of enzymes involved in metabolism. Disruption of circadian rhythms may lead to obesity and metabolic disorders. We tested whether the biological clock controls adiponectin signaling pathway in the liver and whether fasting and/or high-fat (HF) diet affects this control. Mice were fed low-fat or HF diet and fasted on the last day. The circadian expression of clock genes and components of adiponectin metabolic pathway in the liver was tested at the RNA, protein, or enzyme activity level. In addition, serum levels of glucose, adiponectin, and insulin were measured. Under low-fat diet, adiponectin signaling pathway components exhibited circadian rhythmicity. However, fasting and HF diet altered this circadian expression; fasting resulted in a phase advance, and HF diet caused a phase delay. In addition, adenosine monophosphate-activated protein kinase levels were high during fasting and low during HF diet. Changes in the phase and daily rhythm of clock genes and components of adiponectin signaling pathway as a result of HF diet may lead to obesity and may explain the disruption of other clock-controlled output systems, such as blood pressure and sleep/wake cycle, usually associated with metabolic disorders.
Adiponectin signaling pathway components exhibit circadian rhythmicity under low-fat diet. Fasting and high-fat diet alter this circadian expression, leading to phase advance and delay, respectively.
House mice (Mus musculus) and laboratory strains of rats (Rattus norvegicus) have been traditionally considered nonphotoperiodic because their reproductive systems are unaffected by day length (photoperiod). In rats, however, at least three experimental manipulations, perinatal testosterone injection, chronic peripubertal testosterone exposure, or peripubertal olfactory bulbectomy, have revealed latent reproductive photoperiodism. The effectiveness of these experimental treatments may be unique to albino rats. Alternatively, these experimental manipulations may unmask the ability to discriminate short from long days in several "nonphotoperiodic" species and, thus, reveal clues to common physiological mechanisms underlying reproductive responsiveness to photoperiod. In the present study, male house mice were 1) subjected to olfactory bulbectomy or a sham operation at 23 days of age, 2) injected with testosterone or the oil vehicle at 3 days of age, or 3) implanted subcutaneously with an empty Silastic capsule or one filled with testosterone at 22 days of age. All mice were subsequently housed either in LD 16:8 or LD 4:20 photoperiods. The physiological mechanisms necessary to discriminate long from short day lengths are extant in house mice. Testicular mass was significantly reduced in short-day bulbectomized males when assessed 6 weeks postoperatively, but not when measured 10 weeks after surgery. Similarly, mice injected with testosterone when 3 days old and reared in short days had smaller testes as compared to testosterone-treated males housed in long days. Mice implanted with testosterone capsules regressed their reproductive systems regardless of photoperiod. Other reproductive organ weights followed the same general pattern of results as for testicular mass.(ABSTRACT TRUNCATED AT 250 WORDS)
Pineal melatonin content at several times during the day and night was measured in 36 inbred strains of mice (Mus musculus) kept under LD 12:12 cycles. The results have indicated that only five inbred strains have pineal melatonin content, with higher levels during the night and lower levels during the day; the other 31 strains do not contain detectable melatonin in their pineal gland at any of times examined. The former group includes two commonly used strains (C3H/He and CBA/Ms) and three wild-derived strains (Mol-A, Mol-Nis, MOM). C3H and CBA mice showed a similar pattern of pineal melatonin rhythm with a peak at 2 hours before lights on. The peak levels were about 150 pg/gland in both strains. The rhythmic patterns of melatonin content in Mol-A, Mol-Nis, and MOM were slightly different from those in CBA and C3H. In the wild-derived strains, the peak of melatonin content did not occur at 2 hours before lights on but tended to occur at midnight. The peak levels were 67-91 pg/gland at the highest point in these strains.
This study examines the effects of long-term continuous exposure to light on dopaminergic supersensitivity induced by repeated treatment with haloperidol in rats.
Spontaneous general activity in an open-field (SGA) and stereotyped behavior induced by apomorphine (SB-APO) or amphetamine (SB-AMP) were used as experimental parameters. Rats were allocated to four groups in each experiment: saline-treated animals kept under a 12-hour light/dark cycle (LD) or 24-hour light/light cycle (LL), and 2 mg/kg haloperidol-treated animals kept under the above cycles. Plasma corticosterone concentration was also measured by radioimmunoassay in saline-treated rats kept under a LD or LL cycle.
All the behavioral parameters used showed the development of central dopaminergic supersensitivity in rats kept under both cycles. Continuous exposure to light enhanced SGA and SB-AMP in both saline- and haloperidol-treated rats, but did not modify SB-APO. Animals kept under the LL cycle presented an increased plasma corticosterone concentration.
Our results suggest that continuous exposure to light leads to an increase in dopaminergic function in both normal and "supersensitive" rats. This effect seems to be mediated by a presynaptic mechanism possibly involving corticosterone actions.
An elevated cardiovascular disease risk for shiftworkers has frequently been reported, however, the mechanism is still unknown. Changes in eating habits, in physical activity or metabolic factors could be involved. In this study we assessed the relationship between body mass index (BMI) as a possible indicator of changed eating habits or metabolic involvement and duration of shiftwork.
Data from an ongoing cohort study among 377 shiftworkers and non-shiftworking controls, all starting in a new job were used. Anthropometric measurements were carried out at the start of the assignment. Job history was obtained by a questionnaire.
A positive relationship was observed between BMI and waist to hip ratio (WHR) and duration of shiftwork experience, with an adjustment for age. The linear regression coefficients, with additional adjustments for sex, smoking status, physical activity and educational level were 0.12 kg/m2 per y in shiftwork for BMI (P<0.05) and 0.0016 per y in shiftwork for WHR (P<0.05).
These results suggest a relationship between years worked in shifts with BMI and WHR for both males and females. Whether this might reflect an effect of changed dietary habits or a metabolic effect is not yet clear.
The benefits of physical activity in reducing cardiovascular disease (CVD) are thought to be mediated through changes in blood lipids, insulin sensitivity, and thrombogenic factors. Few studies have addressed the effects of both long-term physical activity and inactivity on these factors. The authors assessed associations between long-term leisure-time physical activity, television watching, and biomarkers of CVD risk among 468 healthy male health professionals. Prior to blood collection in 1993-1994, physical activity and television watching were assessed biennially from 1986 to 1994 by a questionnaire. Physical activity was expressed as metabolic equivalents-hours per week. Multivariate linear regression analyses showed that metabolic equivalents-hours in 1994 were significantly associated with high density lipoprotein cholesterol (HDL cholesterol) (positively) and with leptin and C-peptide (inversely). The average number of hours of television watching assessed in 1994 was significantly positively associated with low density lipoprotein cholesterol and significantly inversely associated with HDL cholesterol and apolipoprotein A1. Average hours of television watching per week assessed in 1988-1994 was positively associated with leptin levels (p < 0.01). The associations of television watching and vigorous activity with leptin and HDL cholesterol were independent of each other. In conclusion, physical activity and television watching were significantly associated with several biochemical markers of obesity and CVD risk.
In mammals, a master circadian "clock" resides in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN clock is composed of multiple, single-cell circadian oscillators, which, when synchronized, generate coordinated circadian outputs that regulate overt rhythms. Eight clock genes have been cloned that are involved in interacting transcriptional-/translational-feedback loops that compose the molecular clockwork. The daily light-dark cycle ultimately impinges on the control of two clock genes that reset the core clock mechanism in the SCN. Clock-controlled genes are also generated by the central clock mechanism, but their protein products transduce downstream effects. Peripheral oscillators are controlled by the SCN and provide local control of overt rhythm expression. Greater understanding of the cellular and molecular mechanisms of the SCN clockwork provides opportunities for pharmacological manipulation of circadian timing.