Differences in Daily Rhythms of Wrist Temperature Between Obese and Normal-Weight Women: Associations With Metabolic Syndrome Features

The circadian rhythm of core body temperature is associated with widespread physiological effects. However, studies with other more practical temperature measures, such as wrist (WT) and proximal temperatures, are still scarce. The aim of this study was to investigate whether obesity is associated with differences in mean WT values or in its daily rhythmicity patterns. Daily patterns of cortisol, melatonin, and different metabolic syndrome (MetS) features were also analyzed in an attempt to clarify the potential association between chronodisruption and MetS. The study was conducted on 20 normal-weight women (age: 38?±?11 yrs and BMI: 22?±?2.6?kg/m²) and 50 obese women (age: 42?±?10 yrs and BMI: 33.5?±?3.2?kg/m²) (mean?±?SEM). Skin temperature was measured over a 3-day period every 10?min with the “Thermochron iButton.” Rhythmic parameters were obtained using an integrated package for time-series analysis, “Circadianware.” Obese women displayed significantly lower mean WT (34.1°C?±?0.3°C) with a more flattened 24-h pattern, a lower-quality rhythm, and a higher intraday variability (IV). Particularly interesting were the marked differences between obese and normal-weight women in the secondary WT peak in the postprandial period (second-harmonic power [P2]), considered as a marker of chronodisruption and of metabolic alterations. WT rhythmicity characteristics were related to MetS features, obesity-related proteins, and circadian markers, such as melatonin. In summary, obese women displayed a lower-quality WT daily rhythm with a more flattened pattern (particularly in the postprandial period) and increased IV, which suggests a greater fragmentation of the rest/activity rhythm compared to normal-weight women. These 24-h changes were associated with higher MetS risk. (Author correspondence: garaulet@um.es)     

Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62-72 yrs) and 9 older good-sleeping women (60-82 yrs) were compared with 10 younger good-sleeping women (23-28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00?h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00?h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00?h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00?h than older good sleepers (mean?±?SD: 7.0?±?9.63 pg/mL vs. 15.6?±?24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10?h) and older (19:57?h) good-sleeping women, but was delayed ～50?min in older poor-sleeping women (20:47?h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R(2)?=?0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people.     

The daily melatonin pattern in Djungarian hamsters depends on the circadian phenotype

Djungarian hamsters (Phodopus sungorus) bred at the Institute of Halle reveal three different circadian phenotypes. The wild type (WT) shows normal locomotor activity patterns, whereas in hamsters of the DAO (delayed activity onset) type, the activity onset is continuously delayed. Since the activity offset in those hamsters remains coupled to "light-on," the activity time becomes compressed. Hamsters of the AR (arrhythmic) type are episodically active throughout the 24 h. Previous studies showed that a disturbed interaction of the circadian system with the light-dark (LD) cycle contributes to the phenomenon observed in DAO hamsters. To gain better insight into the underlying mechanisms, the authors investigated the daily melatonin rhythm, as it is a reliable marker of the circadian clock. Hamsters were kept individually under standardized laboratory conditions (LD 14:10, T=22°C±2°C, food and water ad libitum). WT, DAO (with exactly 5 h delay of activity onset), and AR hamsters were used for pineal melatonin and urinary 6-sulfatoxymelatonin (aMT6s) measurement. Pineal melatonin content was determined at 3 time points: 4 h after "light-off" [D+4], 1 h before "light-on" [L-1], and 1h after "light-on" [L+1]). The 24-h profile of melatonin secretion was investigated by transferring the animals to metabolic cages for 27?h to collect urine at 3-h intervals for aMT6s analysis. WT hamsters showed high pineal melatonin content during the dark time (D+4, L-1), which significantly decreased at the beginning of the light period (L+1). In contrast, DAO hamsters displayed low melatonin levels during the part of the dark period when animals were still resting (D+4). At the end of the dark period (L-1), melatonin content increased significantly and declined again when light was switched on (L+1). AR hamsters showed low melatonin levels, comparable to daytime values, at all 3 time points. The results were confirmed by aMT6s data. WT hamsters showed a marked circadian pattern of aMT6s excretion. The concentration started to increase 3?h after "light-off" and reached daytime values 5 h after "light-on." In DAO hamsters, in contrast, aMT6s excretion started about 6?h later and reached significantly lower levels compared to WT hamsters. In AR animals, aMT6s excretion was low at all times. The results clearly indicate the rhythm of melatonin secretion in DAO hamsters is delayed in accord with their delayed activity onset, whereas AR hamsters display no melatonin rhythm at all. Since the regulatory pathways for the rhythms of locomotor activity and melatonin synthesis (which are downstream from the suprachiasmatic nucleus [SCN]) are different but obviously convey the same signal, we conclude that the origin of the phenomenon observed in DAO hamsters must be located upstream of the SCN, or in the SCN itself.     

Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3-12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00-06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=?-2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats.     

Crosstalk between environmental light and internal time in humans

Daily exposure to environmental light is the most important zeitgeber in humans, and all studied characteristics of light pattern (timing, intensity, rate of change, duration, and spectrum) influence the circadian system. However, and due to lack of current studies on environmental light exposure and its influence on the circadian system, the aim of this work is to determine the characteristics of a naturalistic regimen of light exposure and its relationship with the functioning of the human circadian system. Eighty-eight undergraduate students (18-23 yrs) were recruited in Murcia, Spain (latitude 38°01'N) to record wrist temperature (WT), light exposure, and sleep for 1 wk under free-living conditions. Light-exposure timing, rate of change, regularity, intensity, and contrast were calculated, and their effects on the sleep pattern and WT rhythm were then analyzed. In general, higher values for interdaily stability, relative amplitude, mean morning light, and light quality index (LQI) correlated with higher interdaily stability and relative amplitude, and phase advance in sleep plus greater stability in WT and phase advance of the WT circadian rhythm. On the other hand, a higher fragmentation of the light-exposure rhythm was associated with more fragmented sleep. Naturalistic studies using 24-h ambulatory light monitoring provide essential information about the main circadian system input, necessary for maintaining healthy circadian tuning. Correcting light-exposure patterns accordingly may help prevent or even reverse health problems associated with circadian disruption.     

The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes

Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100?mg?day^?1 of melatonin or placebo 30?min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00?h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep–wake cycle, improving sleep efficiency.     

Internal rhythms in humans

Human physiology and behavior are characterized by a daily internal temporal dimension. This so-called circadian rhythmicity is present for almost all variables studied to date, persists in the absence of external cycles, and is synchronized to the external 24-h world by an internally generated circadian rhythm of light sensitivity. The light-sensitive circadian pacemaker, presumably also in humans located in the suprachiasmatic nucleus of the hypothalamus, drives the endogenous circadian component of rhythmicity for a number of variables including plasma melatonin, alertness, sleep propensity and sleep structure. Overt rhythmicity and the consolidation of vigilance states are generated by a fine-tuned interaction of this circadian process with other regulatory processes such as sleep homeostasis.     

Effect of sleep apnea syndrome on the circadian profile of cortisol in obese men

It has been hypothesized that sleep apnea syndrome (SAS) increases hypothalamic-pituitary-adrenal axis activity and, through increased cortisol levels, participates in the pathophysiology of metabolic and cardiovascular complications. We compared the circadian profiles of cortisol in obese men with [obSAS+; apnea-hypopnea index (AHI) >or= 20/h] and without SAS (obSAS-; AHI 相似文献   

Lateral wedges decrease biomechanical risk factors for knee osteoarthritis in obese women

Obesity is the primary risk factor for the development and progression of medial compartment knee osteoarthritis. Laterally wedged insoles can reduce many of the biomechanical risk factors for disease development in osteoarthritis patients and lean individuals but their efficacy is unknown for at-risk, obese women. The purpose was to determine how an 8° laterally wedged insole influenced kinetic and kinematic gait parameters in obese women. Gait analysis was performed on fourteen obese (average 29.3 years; BMI 37.2kg/m(2)) and 14 lean control women (average 26.1 years; BMI 22.4kg/m(2)) with and without a full-length, wedged insole. Peak joint angles, the external knee adduction moment and its angular impulse were calculated during preferred and standard 1.24m/s walking speeds. Statistical significance was assessed using a 2-way ANOVA (α=0.05). The insole significantly reduced the peak external knee adduction moment (mean decrease of 3.6±3.9Nm for obese and 1.9±1.8Nm for controls) and its angular impulse in both groups. The wedged insoles also produced small changes in ankle dorsiflexion (obese: 1.2±1.4° increase; control: 1.5±1.4° increase) and eversion range of motion (obese: 1.3±1.9° decrease; control: 1.5±1.2° decrease) but did not alter peak angles of superior joints. Although the majority of obese women may develop knee osteoarthritis during their lifetime, a prophylactic insole intervention could allow obese women with no severe knee malalignments to be active while preventing or delaying disease onset. However, the long-term effects of the insole have not yet been examined.     

A method to evaluate dynamics and periodicity of hormone secretion

Spontaneous hormone secretory dynamics include tonic and pulsatile components and a number of periodic processes. Circadian variations are usually found for melatonin, TSH and GH, with peak secretions at night, and in cortisol secretion, which peaks in the morning. Free thyroxine (FT4) and insulin-like growth factor (IGF)1 levels do not always change with circadian rhythmicity or show only minor fluctuations. Fractional variations explore the dynamics of secretion related to time intervals, and the rate of change in serum levels represents a signal for the receptorial system and the target organ. We evaluated time-related variations and change dynamics for melatonin, cortisol, TSH, FT4, GH and IGF1 levels in blood samples obtained every 4 h for 24 h from eleven healthy males, ages 35-53 years (mean ? SE 43.6 ± 1.7). Nyctohemeral (i.e., day-night) patterns of hormone secretion levels and the fractional rate of variation between consecutive 4-hourly time-qualified hormone serum levels (calculated as percent change from time 1 to time 2) were evaluated for circadian periodicity using a 24 and 12-h cosine model. A circadian rhythm was validated for serum level changes in cortisol with peaks of the 24-h cosine model at 07:48 h, and melatonin, TSH and GH, with phases at 01:35 h, 23:32 h, and 00:00 h, respectively. A weak, but significant, 12-h periodicity was found for FT4 serum levels, with minor peaks in the morning (10:00 h) and evening (22:00 h), and for IGF1, with minor peaks in the morning (07:40 h) and evening (19:40 h). Circadian rhythmicity was found in the 4-hourly fractional variations with phases of increase or surge at 02:00 h for cortisol, 22:29 h for melatonin, 05:14 h for FT4, and 21:19 h for GH. A significant 12-h periodicity was found for the 4-hourly fractional variations of TSH with two peaks in the morning (decrease or drop at 04:42 h) and afternoon (surge at 16:28 h), whereas IGF1 fractional variation changes did not show a significant rhythmic pattern. In conclusion, the calculation of the time-qualified fractional rate of variation allows evaluation of the dynamics of secretion and the specification of the timepoint(s) of maximal change of secretion, not only for hormones whose secretion is characterized by a circadian pattern of variation, but also for hormones that show no circadian or only weak ultradian (12 h) variations (i.e., FT4).     

Effect of menopause on melatonin and alertness rhythms investigated in constant routine conditions

Although studies have reported the effects of the menstrual cycle on melatonin rhythmicity, none has investigated the effects of menopause on the melatonin rhythm. The circadian rhythm in melatonin and its relationship to subjective alertness was investigated in pre- and postmenopausal women under constant routine conditions (controlled posture, dim lighting, calorie intake, temperature, and prolonged wakefulness). Eleven healthy pre-menopausal (42+/-4 yr) and 10 postmenopausal women (55+/-2 yr) participated in the study. Salivary melatonin samples and subjective measures of alertness and sleepiness were assessed hourly during the 22 h constant routine protocol. Postmenopausal women had a significantly earlier melatonin acrophase (1.1+/-0.5 h clock time in decimal h; mean+/-SEM, p<0.05) compared to the pre-menopausal women (2.3+/-0.3 h). There was no significant difference between melatonin onset and amplitude between the pre-menopausal and postmenopausal women. Self-rated alertness declined in both study groups as the length of sleep deprivation increased. Melatonin onset preceded the onset of self-rated sleepiness in both groups. The time interval between melatonin onset and the onset of sleepiness and alertness offset was significantly greater in the postmenopausal women compared to the pre-menopausal women. In conclusion, under controlled experimental conditions the timing of the melatonin rhythm was advanced in postmenopausal women altering its phase relationship to subjective alertness and sleepiness.     

Twenty-four-hour rhythm patterns of plasma melatonin in short-day and long-day breeders maintained under natural environmental conditions

ABSTRACT

Photoperiodic treatments have been of practical interest in controlling seasonal reproduction in sheep, goats and horses. Melatonin is the principal mediator of the environmental photoperiodic message. To investigate the intra- and inter-subject variability of melatonin 24 h rhythm, ten female Italian Saddle horses (8–10 yrs old, mean body weight 525 ± 30 kg), ten female Sarda breed sheep (2–3 yrs old, mean body weight 40.5 ± 2.8 kg) and ten female Sarda breed goats (3–4 yrs old, mean body weight 38.9 ± 4.1 kg), housed individually in a 4 × 4 m soundproof box equipped with 50 × 100 cm opening windows, were subjected to a natural photoperiod of the vernal equinox (sunrise 06:00 h; sunset 18:00 h). Blood samples were collected from each animal, every 3 h over a 48 h period starting at 00:00 h of day 1 and ending at 00:00 h of day 3. Plasma melatonin concentrations were determined by direct radioimmunoassay (MelatoninDirect RIA, Labor Diagnostika Nord GmbH, Nordhorn, Germany). The application of single cosinor method substantiated a circadian rhythm of melatonin with a nocturnal peak in all studied species. The application of two-way ANOVA on the rhythmic parameters indicated statistically significant differences between the three species in all of the cosinor analysis-derived parameters of MESOR, amplitude, acrophase and robustness of rhythm. Analyses of intra- and inter-subject variability indicate that organization of the melatonin 24 h rhythm is characterized by great accuracy of control within and between the individuals of a breed. In conclusion, features of the 24 h rhythm of melatonin among species; however, the 24 h rhythmicity of melatonin each species showed high stability within the various subjects and within the same subject. These findings must be taken into consideration when applying photoperiod and melatonin treatments for breeding purposes.     

Timed maternal melatonin treatment reverses circadian disruption of the fetal adrenal clock imposed by exposure to constant light

Surprisingly, in our modern 24/7 society, there is scant information on the impact of developmental chronodisruption like the one experienced by shift worker pregnant women on fetal and postnatal physiology. There are important differences between the maternal and fetal circadian systems; for instance, the suprachiasmatic nucleus is the master clock in the mother but not in the fetus. Despite this, several tissues/organs display circadian oscillations in the fetus. Our hypothesis is that the maternal plasma melatonin rhythm drives the fetal circadian system, which in turn relies this information to other fetal tissues through corticosterone rhythmic signaling. The present data show that suppression of the maternal plasma melatonin circadian rhythm, secondary to exposure of pregnant rats to constant light along the second half of gestation, had several effects on fetal development. First, it induced intrauterine growth retardation. Second, in the fetal adrenal in vivo it markedly affected the mRNA expression level of clock genes and clock-controlled genes as well as it lowered the content and precluded the rhythm of corticosterone. Third, an altered in vitro fetal adrenal response to ACTH of both, corticosterone production and relative expression of clock genes and steroidogenic genes was observed. All these changes were reversed when the mother received a daily dose of melatonin during the subjective night; supporting a role of melatonin on overall fetal development and pointing to it as a 'time giver' for the fetal adrenal gland. Thus, the present results collectively support that the maternal circadian rhythm of melatonin is a key signal for the generation and/or synchronization of the circadian rhythms in the fetal adrenal gland. In turn, low levels and lack of a circadian rhythm of fetal corticosterone may be responsible of fetal growth restriction; potentially inducing long term effects in the offspring, possibility that warrants further research.     

Neuro-endocrine correlations of hypothalamic-pituitary-thyroid axis in healthy humans

Neuro-endocrine hormone secretion is characterized by circadian rhythmicity. Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak in the morning, determining the circadian rhythm of cortisol secretion, TRH and TSH show circadian variations with higher levels at night. Thyroxine levels do not change with clear circadian rhythmicity. In this paper we have considered a possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were determined in blood samples obtained every four hours for 24 hours from ten healthy males, aged 36-51 years. We correlated hormone serum levels at each sampling time and evaluated the presence of circadian rhythmicity of hormone secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated negatively with FT4, TSH correlated positively with TRH, TRH correlated positively with FT4 and melatonin correlated positively with TSH. In the resting phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin correlated negatively with FT4, TSH correlated negatively with FT4, cortisol correlated positively with FT4 and TSH correlated positively with TRH. A clear circadian rhythm was validated for the time-qualified changes of melatonin and TSH secretion (with acrophase during the night), for cortisol serum levels (with acrophase in the morning), but not for TRH and FT4 serum level changes. In conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by cortisol and melatonin serum levels and by their circadian rhythmicity of variation.     

Impact of Chronodisruption during Primate Pregnancy on the Maternal and Newborn Temperature Rhythms

Disruption of the maternal environment during pregnancy is a key contributor to offspring diseases that develop in adult life. To explore the impact of chronodisruption during pregnancy in primates, we exposed pregnant capuchin monkeys to constant light (eliminating the maternal melatonin rhythm) from the last third of gestation to term. Maternal temperature and activity circadian rhythms were assessed as well as the newborn temperature rhythm. Additionally we studied the effect of daily maternal melatonin replacement during pregnancy on these rhythms. Ten pregnant capuchin monkeys were exposed to constant light from 60% of gestation to term. Five received a daily oral dose of melatonin (250 µg kg/body weight) at 1800 h (LL+Mel) and the other five a placebo (LL). Six additional pregnant females were maintained in a 14∶10 light:dark cycles and their newborns were used as controls (LD). Rhythms were recorded 96 h before delivery in the mother and at 4–6 days of age in the newborn. Exposure to constant light had no effect on the maternal body temperature rhythm however it delayed the acrophase of the activity rhythm. Neither rhythm was affected by melatonin replacement. In contrast, maternal exposure to constant light affected the newborn body temperature rhythm. This rhythm was entrained in control newborns whereas LL newborns showed a random distribution of the acrophases over 24-h. In addition, mean temperature was decreased (34.0±0.6 vs 36.1±0.2°C, in LL and control, respectively P<0.05). Maternal melatonin replacement during pregnancy re-synchronized the acrophases and restored mean temperature to the values in control newborns. Our findings demonstrate that prenatal melatonin is a Zeitgeber for the newborn temperature rhythm and supports normal body temperature maintenance. Altogether these prenatal melatonin effects highlight the physiological importance of the maternal melatonin rhythm during pregnancy for the newborn primate.     

Feeding melatonin enhances the phase shifting response to triazolam in both young and old golden hamsters

Aging alters many aspects of circadian rhythmicity, including responsivity to phase-shifting stimuli and the amplitude of the rhythm of melatonin secretion. As melatonin is both an output from and an input to the circadian clock, we hypothesized that the decreased melatonin levels exhibited by old hamsters may adversely impact the circadian system as a whole. We enhanced the diurnal rhythm of melatonin by feeding melatonin to young and old hamsters. Animals of both age groups on the melatonin diet showed larger phase shifts than control-fed animals in response to an injection with the benzodiazepine triazolam at a circadian time known to induce phase advances in the activity rhythm of young animals. Thus melatonin treatment can increase the sensitivity of the circadian timing system of young animals to a nonphotic stimulus, and the ability to increase this sensitivity persists into old age, indicating exogenous melatonin might be useful in reversing at least some age-related changes in circadian clock function.     

Crosstalk Between Environmental Light and Internal Time in Humans

Daily exposure to environmental light is the most important zeitgeber in humans, and all studied characteristics of light pattern (timing, intensity, rate of change, duration, and spectrum) influence the circadian system. However, and due to lack of current studies on environmental light exposure and its influence on the circadian system, the aim of this work is to determine the characteristics of a naturalistic regimen of light exposure and its relationship with the functioning of the human circadian system. Eighty-eight undergraduate students (18–23 yrs) were recruited in Murcia, Spain (latitude 38°01′N) to record wrist temperature (WT), light exposure, and sleep for 1 wk under free-living conditions. Light-exposure timing, rate of change, regularity, intensity, and contrast were calculated, and their effects on the sleep pattern and WT rhythm were then analyzed. In general, higher values for interdaily stability, relative amplitude, mean morning light, and light quality index (LQI) correlated with higher interdaily stability and relative amplitude, and phase advance in sleep plus greater stability in WT and phase advance of the WT circadian rhythm. On the other hand, a higher fragmentation of the light-exposure rhythm was associated with more fragmented sleep. Naturalistic studies using 24-h ambulatory light monitoring provide essential information about the main circadian system input, necessary for maintaining healthy circadian tuning. Correcting light-exposure patterns accordingly may help prevent or even reverse health problems associated with circadian disruption. (Author correspondence: angerol@um.es)     

Circadian phase, sleepiness, and light exposure assessment in night workers with and without shift work disorder

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean ± SD] age: 39.2 ± 12.5 yrs; mean yrs on shift = 9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6 ± 8.6 yrs; mean years on shift = 8.4) participated. All participants were admitted to the sleep center at 16:00 h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00 h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42 ± 3.25 h, whereas in the SWD group it was 20:42 ± 2.21 h (z = 2.4; p 相似文献   

CLOCK,PER2 and BMAL1 DNA Methylation: Association with Obesity and Metabolic Syndrome Characteristics and Monounsaturated Fat Intake

The circadian clock system instructs 24-h rhythmicity on gene expression in essentially all cells, including adipocytes, and epigenetic mechanisms may participate in this regulation. The aim of this research was to investigate the influence of obesity and metabolic syndrome (MetS) features in clock gene methylation and the involvement of these epigenetic modifications in the outcomes. Sixty normal-weight, overweight and obese women followed a 16-weeks weight reduction program. DNA methylation levels at different CpG sites of CLOCK, BMAL1 and PER2 genes were analyzed by Sequenom's MassARRAY in white blood cells obtained before the treatment. Statistical differences between normal-weight and overweight?+?obese subjects were found in the methylation status of different CpG sites of CLOCK (CpGs 1, 5-6, 8 and 11-14) and, with lower statistical significance, in BMAL1 (CpGs 6-7, 8, 15 and 16-17). The methylation pattern of different CpG sites of the three genes showed significant associations with anthropometric parameters such as body mass index and adiposity, and with a MetS score. Moreover, the baseline methylation levels of CLOCK CpG 1 and PER2 CpGs 2-3 and 25 correlated with the magnitude of weight loss. Interestingly, the percentage of methylation of CLOCK CpGs 1 and 8 showed associations with the intake of monounsaturated and polyunsaturated fatty acids. This study demonstrates for the first time an association between methylation status of CpG sites located in clock genes (CLOCK, BMAL1 and PER2) with obesity, MetS and weight loss. Moreover, the methylation status of different CpG sites in CLOCK and PER2 could be used as biomarkers of weight-loss success, particularly CLOCK CPGs 5-6. (Author correspondence: garaulet@um.es)     

Circadian Pattern of Serum Leptin and ß-Endorphin Levels in Obese and Non Obese Women

To investigate diurnal profile of leptin and ß-endorphin circulating levels and to assess any possible influence between these two peptides, 24–h serum concentrations of leptin and ß-endorphin were examined in 24 obese (BMI 32.1 ± 1.3) women and in 12 controls (BMI 21 ± 0.5). Blood samples for leptin and ß-endorphin determinations were drawn every four hours for 24 hours beginning at 8.00 am. Data were analyzed by unpaired t-test, linear regression and by inferential statistical procedures. We found a significant circadian rhythm for both peptides, either in obese or in controls. The 24–h mean leptin levels were significantly (p &lt; 0.0001) higher (32.1 ± 2.8ng/ml; mean ± SE) in obese women than controls (13.6 ± 1.1), with a peak time located after midnight in obese and controls. The 24–h ß-endorphin mean levels were significantly (p &lt; 0.0001) higher in obese than controls (30.6 ± 2 vs 22 ± 1.9pg/ml), with acrophase located in the early morning hours in both groups. Finally, we found a positive relationship (R 2 = 0.303; p = 0.0005) between leptin and ß-endorphin circadian mean levels. These results show that the time course of 24–h rhythm of leptin and ß-endorphin are similar in obese and lean women. The positive relationship between 24–h leptin and ß-endorphin mean levels allow us to speculate that leptin may be a likely candidate to increase ß-endorphin levels in obese subjects.