Does a high-fat diet affect the circadian clock,or is it the other way around? A systematic review

This paper reviews studies that addressed the influence of diet on circadian rhythmicity in mice and, in turn, circadian clock chronodisruption and its role in the development of metabolic disorders. Studies from the past 14 years were selected via a systematic search conducted using the PubMed electronic database. After applying the inclusion and exclusion criteria, 291 studies were selected, of which 13 were chosen using the following inclusion criteria: use of a high-fat diet for mice, evaluation of clock gene expression, and the association between chronodisruption and lipid metabolism disorders. These studies reported changes in animals' biological clock when they developed metabolic disorders by consuming a high-fat diet. It was also evident that some clock gene mutations or deletions triggered metabolic changes. Disturbances of clock gene machinery may play important roles in lipid metabolism and the development of atherosclerotic processes. However, many metabolic processes also affect the function of clock genes and circadian systems. In summary, this review's results may provide new insights into the reciprocal regulation of energy homeostasis and the biological clock.     

From clock genes to telomeres in the regulation of the healthspan

Biological clocks are classified into oscillatory (clock genes) and unidirectional hourglass clocks (telomeres). Clock genes align behavioral and biochemical processes with the day/night cycle. Telomeres, the repeated series of DNA sequences that cap the ends of chromosomes, become shorter during cell division. Shortened telomeres have been documented in various pathological states associated with aging. Human activity is driven by NADH and ATP produced from nutrients, and the resulting NAD and AMP play a predominant role in energy regulation. Caloric restriction increases both AMP and NAD and is known to extend the healthspan (healthy lifespan) of animals. Silent information regulator T1 (SIRT1), the NAD-dependent deacetylase, attenuates telomere shortening, while peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a master modulator of gene expression, is phosphorylated by AMP kinase and deacetylated by SIRT1. Thus, PGC-1α is a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism. Reactive oxygen species produced in clock mutants result in telomere shortening. The circadian rhythms produced by clock genes and lifestyle factors are ultimately controlled by the human brain and drive homeostatic and hedonic feeding and daily activity.     

Postnatal ontogenesis of clock genes in mouse suprachiasmatic nucleus and heart

Background  

The master clock within the hypothalamic suprachiasmatic nucleus (SCN) synchronizing clocks in peripheral tissues is entrained by the environmental condition, such as the light-dark (LD) cycle. The mechanisms of circadian clockwork are similar in both SCN and peripheral tissues. The aim of the present work was to observe the profiles of clock genes expression in mouse central and peripheral tissues within postnatal day 5 (P5). The daily expression of four clock genes mRNA (Bmal1, Per2, Cry1 and Rev-erb alpha) in mouse SCN and heart was measured at P1, P3 and P5 by real-time PCR.     

Chronobiology and Obesity: Interactions between Circadian Rhythms and Energy Regulation

Recent advances in the understanding of the molecular, genetic, neural, and physiologic basis for the generation and organization of circadian clocks in mammals have revealed profound bidirectional interactions between the circadian clock system and pathways critical for the regulation of metabolism and energy balance. The discovery that mice harboring a mutation in the core circadian gene circadian locomotor output cycles kaput (Clock) develop obesity and evidence of the metabolic syndrome represented a seminal moment for the field, clearly establishing a link between circadian rhythms, energy balance, and metabolism at the genetic level. Subsequent studies have characterized in great detail the depth and magnitude of the circadian clock’s crucial role in regulating body weight and other metabolic processes. Dietary nutrients have been shown to influence circadian rhythms at both molecular and behavioral levels; and many nuclear hormone receptors, which bind nutrients as well as other circulating ligands, have been observed to exhibit robust circadian rhythms of expression in peripheral metabolic tissues. Furthermore, the daily timing of food intake has itself been shown to affect body weight regulation in mammals, likely through, at least in part, regulation of the temporal expression patterns of metabolic genes. Taken together, these and other related findings have transformed our understanding of the important role of time, on a 24-h scale, in the complex physiologic processes of energy balance and coordinated regulation of metabolism. This research has implications for human metabolic disease and may provide unique and novel insights into the development of new therapeutic strategies to control and combat the epidemic of obesity.     

Evidence for clock genes circadian rhythms in human full-term placenta

Abstract

Biological rhythms are driven by endogenous biological clocks; in mammals, the master clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This master pacemaker can synchronize other peripheral oscillators in several tissues such as some involved in endocrine or reproductive functions. The presence of an endogenous placental clock has received little attention. In fact, there are no studies in human full-term placentas. To test the existence of an endogenous pacemaker in this tissue we have studied the expression of circadian locomoter output cycles kaput (Clock), brain and muscle arnt-like (Bmal)1, period (Per)2, and cryptochrome (Cry)1 mRNAs at 00, 04, 08, 12, 16, and 20 hours by qPCR. The four clock genes studied are expressed in full-term human placenta. The results obtained allow us to suggest that a peripheral oscillator exists in human placenta. Data were analyzed using Fourier series where only the Clock and Bmal1 expression shows a circadian rhythm.     

Polyporus and Bupleuri radix effectively alter peripheral circadian clock phase acutely in male mice

In mammals, daily physiological events are precisely regulated by an internal circadian clock system. An important function of this system is to readjust the phase of the clock daily. In Japan, traditional herb medicines, so-called crude drugs (Shoyaku), are widely used for many diseases, and some are reported to affect circadian clock impairment, suggesting that some of them might have an ability to modify clock gene expression rhythms. Therefore, from selected 40 crude drugs, finding candidates that control the circadian clock phases was the first purpose of this study. As there are several crude drugs used for liver- and/or kidney-related diseases, the second aim of the present study was to find some crude drugs affecting liver/kidney circadian clock in vivo. To assess phase changes in the daily circadian rhythm, bioluminescence from the core clock gene product Period 2 was continuously monitored in mouse embryonic fibroblasts in vitro and in some peripheral tissues (kidney, liver, and submandibular gland) of PERIOD2::LUCIFERASE knock-in mice in vivo. In our screening, Polyporus and Bupleuri radix were found to be good candidates to effectively manipulate the peripheral circadian clock phase acutely, with stimulation time-of-day dependency in vitro as well as in vivo. Interestingly, Polyporus and Bupleuri radix are traditional herb medicines use for treating edema and promoting diuresis, and for chronic hepatitis, respectively. These crude drugs may be therefore good modulators of the circadian peripheral clocks including liver and kidney, and circadian clock genes become new molecular targets for these crude drugs.     

病区输液管理主从通信系统的研制

本文介绍了一种以PC系列微机为主机和以8031单片机为监控装置从机、基于RS－485总线标准构成的主从分布式输液管理系统。管理者在护士站的PC机上即能依靠本系统监控病区内全部病人的输液情况。该系统简单、成本低，通用性强。具有一定的应用前景。     

Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag

We used time-restricted feeding (TRF) to investigate whether microbial metabolites and the hunger hormone ghrelin can become the dominant entraining factor during chronic jetlag to prevent disruption of the master and peripheral clocks, in order to promote health. Therefore, hypothalamic clock gene and Agrp/Npy mRNA expression were measured in mice that were either chronically jetlagged and fed ad libitum, jetlagged and fed a TRF diet, or not jetlagged and fed a TRF diet. Fecal short-chain fatty acid (SCFA) concentrations, plasma ghrelin and corticosterone levels, and colonic clock gene mRNA expression were measured. Preventing the disruption of the food intake pattern during chronic jetlag using TRF restored the rhythmicity in hypothalamic clock gene mRNA expression of Reverbα but not of Arntl. TRF countered the changes in plasma ghrelin levels and in hypothalamic Npy mRNA expression induced by chronic jetlag, thereby reestablishing the food intake pattern. Increase in body mass induced by chronic jetlag was prevented. Alterations in diurnal fluctuations in fecal SCFAs during chronic jetlag were prevented thereby re-entraining the rhythmic expression of peripheral clock genes. In conclusion, TRF during chronodisruption re-entrains the rhythms in clock gene expression and signals from the gut that regulate food intake to normalize body homeostasis.     

Circadian Systems in Man and Their Implications

The “biologic clock” found in all organisms accounts for such well-known phenomena in man as the variations over a 24-hour period in hormone secretion, temperature, and many other body functions, as well as jet lag. It has been found that periodic factors in the environment, like light and dark, pace the biologic rhythm but do not act as its immediate cause. Rather, the rhythm seems to be inherent in the organism.     

Central and peripheral regulation of feeding and nutrition by the mammalian circadian clock: implications for nutrition during manned space flight

Circadian clocks have evolved to predict and coordinate physiologic processes with the rhythmic environment on Earth. Space studies in non-human primates and humans have suggested that this clock persists in its rhythmicity in space but that its function is altered significantly in long-term space flight. Under normal circumstances, the clock is synchronized by the light-dark cycle via the retinohypothalamic tract and the suprachiasmatic nucleus. It is also entrained by restricted feeding regimes via a suprachiasmatic nucleus-independent circadian oscillator. The site of this suboscillator (or oscillators) is not known, but new evidence has suggested that peripheral tissues in the liver and viscera may express circadian clock function when forced to do so by restricted feeding schedules or other homeostatic disruptions. New research on the role of the circadian clock in the control of feeding on Earth and in space is warranted.     

Sommeil et nutrition : approche chronobiologique par les rythmes hormonaux

The suprachiasmatic nuclei of the hypothalamus are the site of the master circadian clock in mammals. The suprachiasmatic clock modulates sleep and food intake, so that both do not occur at the same times of the daily cycle. Hormonal rhythms are, to various degrees, under the control of sleep and/or the suprachiasmatic clock. Drastic changes in homeostatic processes of sleep (e.g., sleep deprivation) or calorie intake (e.g., food restriction) can have an impact on the master circadian clock. Moreover, a chronic desynchronization affects sleep and it can also lead to metabolic changes. Interactions between the circadian clock, sleep-wake cycle and food intake are thus complex, and these systems regulate each other. Their alterations are associated with a host of major health problems.     

Role of Chrononutrition in the Antihypertensive Effects of Natural Bioactive Compounds

Hypertension (HTN) is one of the main cardiovascular risk factors and is considered a major public health problem. Numerous approaches have been developed to lower blood pressure (BP) in hypertensive patients, most of them involving pharmacological treatments. Within this context, natural bioactive compounds have emerged as a promising alternative to drugs in HTN prevention. This work reviews not only the mechanisms of BP regulation by these antihypertensive compounds, but also their efficacy depending on consumption time. Although a plethora of studies has investigated food-derived compounds, such as phenolic compounds or peptides and their impact on BP, only a few addressed the relevance of time consumption. However, it is known that BP and its main regulatory mechanisms show a 24-h oscillation. Moreover, evidence shows that phenolic compounds can interact with clock genes, which regulate the biological rhythm followed by many physiological processes. Therefore, further research might be carried out to completely elucidate the interactions along the time–nutrition–hypertension axis within the framework of chrononutrition.     

Albuminuria assessed from first-morning-void urine samples versus 24-hour urine collections as a predictor of cardiovascular morbidity and mortality

Screening for albuminuria has been advocated because it is associated with cardiovascular morbidity and all-cause mortality. The "gold standard" to assess albuminuria is 24-hour urinary albumin excretion (UAE). Because 24-hour urine collection is cumbersome, guidelines suggest measuring albuminuria in a first morning void, either as urinary albumin concentration (UAC) or adjusted for creatinine concentration, the albumin:creatinine ratio (ACR). To decide which albuminuria measure to use in clinical practice, it is essential to know which best predicts clinical outcome. In a sample representative of the Groningen (the Netherlands) population (n = 3,414), the authors compared UAC, ACR, and UAE as predictors of cardiovascular events and all-cause mortality. During a median follow-up of 7.5 years, which ended December 31, 2005, they observed 278 events (a major adverse cardiovascular event or mortality). The area under the receiver operating characteristic curve predicting events was 0.65 for UAE, 0.62 for UAC (P = 0.06 vs. UAE), and 0.66 for ACR (P = 0.80 vs. UAE; P = 0.01 vs. UAC). When sex-specific subgroups were considered, UAE was superior to UAC in predicting outcome (P = 0.04) for females, whereas, for males as well as females, no difference was found between ACR and UAE. To predict cardiovascular morbidity and all-cause mortality, measuring ACR in a first-morning-void urine sample is a good alternative to measuring 24-hour UAE.     

Role of High Energy Breakfast “Big Breakfast Diet” in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 Diabetes

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of β-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., β-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.     

基于双端口RAM的便携式心电监护仪设计

目的：设计基于双端口RAM的双单片机便携式心电监护仪，解决心电监护数据传送的瓶颈问题。方法：双端口RAM芯片具有2套完全独立的数据线、地址线和读写控制线．因而可使2个CPU分时独立访问其内部RAM资源。主单片机在片上RAM缓存采集数据，满200B，打包写入双端口RAM．双端口RAM缓冲区中的数据达到闪存的页容量时，通知从单片机读取数据，从单片机以页编程方式一次写入闪存。结果：解决了双端口RAM的端口争用问题，并讨论了极限采样频率，实现了主、从单片机数据共享，缓存采集信号，即使在较高采样频率下．仍能确保及时、可靠地存储实时信号。结论：便携式心电监护仪中通常使用大容量NAND闪存实时存储采集到的信号．但是由于NAND闪存的数据写入是以页编程为基础．因而限制了前端采样频率的提高。基于双端口RAM的双单片机便携式心电监护仪的设计合理地的解决了心电监护数据传输的瓶颈问题．     

昼夜节律在病毒感染中的作用

昼夜节律是由内源性时钟调节的多个生物过程的日常振荡,调控机体的各种生理变化。节律紊乱会导致多种疾病的发生,包括代谢综合征和癌症等。最近将昼夜节律系统作用研究扩展到了感染的调控,宿主与病原体的相互作用以及由此产生的疾病结局。深入了解昼夜节律系统在调节病毒感染中的作用将为病毒性传染病的致病机理、抗病毒治疗、疫苗研发等提供新的思路。本文就昼夜节律与病毒感染的相互作用进行综述,包括昼夜节律如何影响病毒感染以及病毒如何调节节律以促进自身复制的关键发现,突出昼夜节律的重要性。     

High doses of vitamin E in the treatment of disorders of the central nervous system in the aged.

Oxidative stress is a putative factor in the pathogenesis of many human disorders of the central nervous system. Therefore, antioxidants such as vitamin E have become attractive as therapeutic agents in the treatment of several diseases. In addition, vitamin E seems to play a specific role in the nervous system. As a result, vitamin E has been used in pharmacologic doses in the treatment of disorders such as Parkinson disease, Alzheimer disease, and tardive dyskinesia. One investigation showed that the use of 2000 IU all-rac-alpha-tocopheryl acetate is beneficial in the treatment of Alzheimer disease. Similar doses of vitamin E, however, were not beneficial for delaying the progression of Parkinson disease. In other studies, dosages >/=400 IU vitamin E/d were found to be beneficial in the treatment of tardive dyskinesia, although this finding was not confirmed in a larger cooperative study conducted by the Veterans Administration. Even though the efficacy of vitamin E in the management of cardiovascular disease has been shown, the potential role of vitamin E in the treatment of cerebrovascular disease remains essentially unknown. The experience from 2 large clinical trials involving the oral intake of 2000 IU vitamin E/d suggests that vitamin E is relatively safe at this dosage for periods <2 y. However, the safety and efficacy of supplemental vitamin E over periods of many years in the prevention of neurologic diseases has not been adequately explored.     

Health status in children with diffuse thyroid enlargement under man-made pollution

The paper presents data on lipid and protein metabolic parameters, hormonal profile, physical development, and the cardiovascular system in school children with and without diffuse thyroid enlargement from the industrial centers of the Irkutsk Region. The study has revealed changes in metabolic processes, physical development, and blood circulation in the population of children, which are considered to be manifestations of adaptive processes to environmental factors, primarily chemical ambient air pollution and iodine deficiency.