Skip to main content
Beni-Suef University Journal of Basic and Applied Sciences
Download PDF

Circadian mechanism disruption is associated with dysregulation of inflammatory and immune responses: a systematic review

Beni-Suef University Journal of Basic and Applied Sciences volume 11, Article number: 107 (2022) Cite this article

Abstract

The circadian rhythms are regulated by the circadian clock which is under the control of suprachiasmatic nucleus of hypothalamus. The central and peripheral clocks on different tissue together synchronize to form circadian system. Factors disrupt the circadian rhythm, such as irregular eating patterns, sleep/wake time, night shift work and temperature. Due to the misalignment of central clock components, it has been recognized as the pathophysiology of lifestyle-related diseases mediated by the inflammation such as diabetes, obesity, neurological disorder and hormonal imbalance. Also we discuss the therapeutic effect of time-restricted feeding over diabetes and obesity caused by miscommunication between central and peripheral clock. The genetic and epigenetic changes involve due to the deregulation of circadian system. The aim of the present review is to discuss the circadian mechanisms that are involved in the complex interaction between host and external factors and its disruption is associated with deregulation of inflammatory and immune responses. Hence, we need to understand the mechanism of functioning of our biological clocks so that it helps us treat health-related problems such as jet lags, sleep disorders due to night-time shift work, obesity and mental disturbances. We hope minimal cost behavioural and lifestyle changes can improve circadian rhythms and presumably provide a better health.

Background

Circadian rhythm is derived from the Latin word: circa means ‘approximate’ and dies means ‘day’. It is natural endogenous process of physiological, molecular and behavioural function throughout the day [1, 2]. Circadian rhythms are regulated by circadian clocks, which drive day–night oscillations with a free running period of 24 h [3]. The central and peripheral clocks on different tissues together synchronize to form circadian system. The whole body controller is situated on the hypothalamus of suprachiasmatic nucleus (SCN) in mammals [4]. However, the SCN acts more as a “master synchronizer” than a true pacemaker. The peripheral tissues and cells show similar gene expression of circadian rhythm as seen in SCN circadian rhythm [5, 6].

The mechanism of circadian rhythm is regulated by the transcription–translation feedback loop; CLOCK:BMAL1 are heterodimerized and bind to the promoted site of E-box to initiate the transcription of Per and Cry gene. These genes are translated and form PER:CRY heterodimer complex which inhibit the self-induced CLOCK:BMAL1 transcription [7]

Many factors affect the central clock and peripheral clock such as sleep/wake time, exercise, eating habits, light exposure and temperature. Eating habit is one of the factors that influence our metabolic process. Taking more than three meals in a day or prolonged eating is associated with metabolic syndrome. Restriction of diet in fixed time of period in a day that robust our circadian rhythm [8, 9]. TRF reduces body weight, improves lipid profile, increases insulin sensitivity, reduces glucose level, and decreases the oxidative stress and inflammatory markers [10,11,12]. Therefore, time-restricted feeding (TRF) is a therapeutic strategy for the treatment of metabolic disorders, such as obesity and diabetes [13].

The circadian clock disruption of pancreas-specific causes impaired glucose tolerance leading to increased glucose level in blood (hyperglycaemia), thereby resulting in decreased secretion of insulin [14]. In adipose tissue, the circadian clock disruption causes the reduction or abnormal secretion of fatty acid from adipocytes leading to obesity. This abnormal secretion from the adipose tissues regulates appetite centre of hypothalamus, which increases feeding throughout the day [15].

In jet lag and shift workers, the desynchronization of environment clock and tissue-specific circadian clock cause sleep disturbance and various metabolic disorders. This is because of miscommunication between feeding time and cellular metabolic process, which is directly linked with circadian rhythm [16]. For example, in pancreatic tissue, the loss of circadian gene, such as brain and muscle aryl hydrocarbon receptor nuclear translocator-like (Bmal1), results in decreased secretion of insulin, which leads to diabetes [17]. Circadian clock regulates many metabolic rhythms including glucose and lipid metabolism, and their disruption could promote diabetes, obesity and chronic heart disease (CHD) in many organisms [18,19,20]. The objective of our review is to create the awareness about the effect of circadian clock on the metabolic process and to deliver the message about the circadian clock management that improves the quality of life.

Method

We did all-inclusive literature search following PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analysis] guide (Fig. 1). A systematic electronic database search with NCBI, MEDLINE, Scopus, Google Scholar, PubMed and Web of Science databases was done to retrieve relevant research and review articles in English language only. All articles identified underwent a review to assess relevance against the eligibility criteria. This review process occurred in stages, which initially involved screening the article titles. We screened the articles using keywords like circadian rhythm, suprachiasmatic nucleus, BMAL1, CLOCK, PER, CRY genetics, epigenetics, time restricted feeding, temperature, diabetes, obesity and neurological disorders combined using Boolean operators AND and OR. This review article, which is submitted here as part of project, was approved by the ethical committee of the institution with reference no. 123/IAEC/2019 and project funded by ICMR, New Delhi.

Fig. 1
figure 1

PRISMA flowchart of the systematic review

Full size image

Genetics and epigenetic basis of circadian rhythm

Genetics

Long-term changes in metabolism are directly linked to the chronological changes, such as alteration in glucose homeostasis, which are closely correlated to the clock gene function. In animal studies, a wide range of disturbance in metabolic process includes the deregulation of glucose metabolism that alters the insulin secretion resulting in impaired gluconeogenesis, obesity and metabolic syndrome [21, 22]. Alternative studies of genetically modified or transgenic mice model noticed the frequent change, due to alteration in clock gene function, resulting in abnormal metabolic phenotype [23].

These similar findings have been reported in many human genetic studies as well. The metabolic disorders like T2DM, obesity and metabolic syndrome have been associated with clock gene polymorphism and their associated haplotypes. Although these above studies reveal that the circadian rhythm gene and metabolism are functionally linked, and they are unable to differentiate the tissue-specific clock to overall phenotype. Due to this problem, there is a need for tissue-specific studies, creating local gene disruption by preparing BMAL1 knock-out model. Loss of function of BMAL1 in peripheral tissue is directly linked with change in glucose homeostasis, which leads to diabetes [24, 25].

Heterodimer formation of CLOCK and BMAL1 takes place to initiate transcription factor of core clock gene in mammals. This heterodimer binds rhythmically to the E-box of Period (Per1, Per2, Per3), Cryptochrome (Cry1 and Cry2), Rev-erb (Rev-erbα and Rev-erbβ) and Ror (Rorα, Rorβ and Rorγ) to initiate transcription. Translated PER/CRY repressive complex block the CLOCK: BMAL1-mediated transcription first on-DNA and then off-DNA [18, 19]. BMAL1 expression is regulated by the REV-ERBs and RORs through the repression and activation of its transcription, which promotes sturdiness of circadian oscillations [26, 27]. On rhythmic transcriptional activation of core clock components, CLOCK:BMAL1 regulates the expression of clock-controlled genes to generate the variations. Thus, it regulates the function of circadian rhythm system [28, 29].

It is interesting to know about the mechanism through which CLOCK: BMAL1 controls the expression of its core clock genes and target genes. Studies show that the rhythmic binding of CLOCK:BMAL 1 heterodimer to the promoter site of core clock gene DNA is required for the rhythmic transcription [24, 26, 30]. Recently, it has been shown that rhythmic binding of CLOCK: BMAL1 heterodimer to DNA initiates the removal of nucleosome, thereby generating a chromatin landscape that is favourable for the binding of second transcription factors at its enhancers [31]. Hence, this heterodimer promotes transcription of core clock gene by recruiting transcriptional co-activators, mediator complex and RNA polymerase II [16, 32]. The core clock gene activated by the CLOCK:BMAL1-mediated transcription mechanism is still unclear. Indeed, most of the clock target genes CLOCK:BMAL1 is expressed rhythmically, and a large fraction of the rhythmically expressed target genes are transcribed at night, in antiphase to maximal CLOCK:BMAL1 DNA binding [30]. These evidences suggest that different mechanisms are involved in CLOCK:BMAL1 regulation of transcription of core clock genes, which differ from the regulation of other clock-controlled genes. The circadian clock adds additional mechanisms for the activation of rhythmic gene expression. The binding of heterodimer CLOCK:BMAL1 to the DNA during transcription is capable for the uncoiling of chromatin and initiates transcription, whereas it is insufficient to produce transcriptionally active enhancers. The CLOCK:BMAL1 heterodimer generates a flexible chromatin landscape to rhythmically prime its enhancers for the recruitment of other transcription factors, rather than directly promoting transcription activation [33].

Epigenetic

The epigenetic changes influence the expression of gene without alteration in the nucleotide sequence leading to phenotypic change only. These epigenetic modifications include DNA methylation and modification of histone that amend the local chromatin and effect DNA accessibility and gene transcription (Table 1) [34]. DNA methyltransferase (DNMT) enzyme involves in methylation of DNA CpG sites of nucleotide, which is an important mechanism of transcriptional repression [35]. However, the DNA methylation performance remains ambiguous and disputed. To counter this, ten–eleven translocase (TET) enzymes catalyse DNA demethylation [36]. Another epigenetic modification includes acetylation and deacetylation of histone protein, which is catalysed by the histone acetyltransferases (HATs) and deacetylase (HDACs), respectively. HATs promote unfolding of chromatin during transcription, whereas HDACs are responsible for the chromatin condensation and hence represses transcription [25]. The repressors of gene transcription can access the acetylated open-chromatin structure [37]. Epigenetic modifications are unable to alter the DNA sequence and are not stable and undergo changes towards the exogenous stimuli such as light, diet [38], temperature [39, 40], social interaction [41] and maternal effect [42]. A recent study in mice model revealed that the time-restricted feeding (TRF) intervention decreased the HDAC activity and enhanced the histone acetylation [43]. During the light phase, CLOCK:BMAL1 binds to the DNA to initiate the chromatin modification by histone-modifying enzymes to the promoter region of core clock gene. The histone-modifying enzymes such as HATs and HMTs catalyse the acetylation and methylation, respectively. Histone acetyltransferase mediates the acetylation of histone lysine at positions H3K9 and H3K27 and methylation at H3K4 by histone methyltransferase. The feedback inhibition of clock gene through the binding of PER:CRY heterodimer to the DNA-bound CLOCK: BMAL1 complex is carried out by the additional recruitment of histone demethylases and deacetylases.

Table 1 Gene involved in metabolism and their mechanism of epigenetic modification
Full size table

Time-restricted feeding (TRF) and circadian rhythm

The TRF has many physiological consequences [44]. A study in mice revealed that the everyday TRF for 4 h enhanced the glucose regulation and reduced weight gain [45]. Another study conducted in mice model showed that TRF for 8 h a day prevents high-fat-diet (HFD)-induced obesity [46], 9 h/day TRF results in reduced plasma glucose level and increased sensitivity and level of insulin in type 1 diabetes [47]. The circulatory level of glucose is lowered as well as the expression of PER 2 clock gene of adipose is delayed due to 5-h meal delay effects. Therefore, feeding time of shift worker may help to reset the circadian system. The effect of TRF on obese mice model induced by high-fat diet normalized the gene expression of lipid metabolism in hepatic tissue [46]. In diurnal organisms, TRF controls the expression of many clock control genes in peripheral tissues. It protects from the adverse effect of obesity induced by high-fat diet and also regulates the transcription factors that play critical role during fasting time in gluconeogenesis and deposition of fat in hepatic cells and multiple markers of inflammation are reduced. The complications were generated by high-fat-diet-induced alteration in metabolic pathways, and generation of oxidative stress by reducing antioxidants is reversed by TRF [48].

It is described in the literature that metabolic parameters, i.e. glucose homeostasis, change every day and every time in humans. In healthy people, glucose tolerance decreases in the afternoon causing a condition called “afternoon diabetes”. This metabolic pathway persists in controlled conditions, through changes in insulin signalling mechanism, which is governed by the internal circadian clock system [49]. Similarly, in night the triacylglycerol plasma level is elevated, if HFD has been taken in night as compared to the daytime meal, which is regulated by circadian rhythm [50].

Animal studies have shown the beneficial effect of TRF leading to improvement in the quality of life and provided protection against obesity and metabolic disorders due to consumption of high-fat diet [44]. Studies in rodents have proved that timely eating is a powerful tool for synchronizing peripheral clock. When animals are kept in a 12-h light/dark cycle, the restricted feeding time disrupts the internal synchronization of clocks [51]. In addition, the role of clocks in individual peripheral tissues provides a physiological insight to explain the temporal differences in postprandial responses. Hence, the meal time is very important as changing the life pattern may protect from various diseases and improve life quality and increases life span.

Temperature effects on circadian rhythm

Temperature also influences circadian clock, because of ubiquity of temperature regulatory mechanism and also potential target for therapeutics. All circadian rhythms are temperature-compensated. This important property allows the clock to maintain a stable period of oscillation regardless of the ambient temperature. The change in circadian rhythm with environmental condition is not reliable. Due to variation in the temperature of poikilothermic organisms, the oscillation of circadian rhythm is desynchronized. In hibernating animals, there is lack of day activity during hibernation period, and the internal body temperature of such animals undergoes circadian fluctuations with amplitudes of approximately 1 °C and 5 °C depending on the species [52].

In our biological system, the heat shock mechanism controls the effect of increasing temperature in our metabolic process and circadian clock. Many heat shock factors/proteins (HSF/HSP) such as HSF1, HSF2 and HSF4 initiate the transcription on increasing temperature. The heat shock element present in the promoter site of the stress response gene is transcribed by the binding of initiation HSF [53]. HSP genes contain heat shock elements (HSEs), and once translated, these proteins, chaperone, sequester the HSP from further transcription [54]. The Per2 gene expressions are reducing or lose their function on the exposure of high temperature [55]. Along with being a temperature sensor for phase setting, evidence proves that the circadian clock and heat shock factors are closely related. Although the levels of HSF have not been found to have circadian oscillation, their binding to target motifs certainly does in spite of the absence of temperature cycles [56]. HSEs located on the promoter region of Per2 gene are conserved among various species and expression of HSP gene synchronizes with the Per2 gene [55]. Finally, the temperature affects circadian rhythm through the heat shock response that exhibits both phase and period influence on the circadian clock.

Hormonal effects on circadian rhythm

In vertebrates, the photoperiod message is delivered by hormone melatonin, which is secreted during night/dark [57]. The secretion of melatonin is regulated by the light and dark cycle. This mechanism is present in SCN of hypothalamus [58, 59]. The data from other studies showed that permanent light period affects the significant decrease in melatonin and increase during permanent dark in healthy animals. During afternoon, leptin plasma concentration starts increasing and reaches its peak between midnight and approximately 2:30 a.m. with considerable inter individual variations [60]. The evidence shows that photoperiod influences the circulatory level of leptin and changes in circadian rhythm change the plasma leptin concentration. Many studies conducted on secretion of leptin and melatonin in healthy subjects showed that there is significant negative correlation [61, 62]. Contrary to it, a study conducted by the Cardoso et al. showed that melatonin had a positive role in the production of insulin-stimulated leptin in adipose tissue of rats. In this mechanism, melatonin binds to Gi protein-coupled MT1 (melatonin transporter 1) membrane receptor and potentiates the phosphorylation of insulin receptors and Akt (Protein Kinase B) [63]. Melatonin performs its action by binding to MT1 and MT2 membrane receptors found on the cell membrane which is coupled with G-protein. After binding, it initiates the signal transduction mechanisms. In human beings, these mechanisms have been found in many organs such as brain, heart, hepatic tissue, kidney, intestine, genital organs, adipocytes and skin (Fig. 2) [64,65,66].

Fig. 2
figure 2

Correlation between circadian rhythm and metabolism. a In SCN, circadian clock composed of interlocking feedback loops consists of transcription activators and repressors. b In peripheral tissue, the activation of metabolic pathway by melatonin secretion. cAMP—cyclic AMP, PKA—Protein kinase A, AKT—Protein kinase B, S6K1-S6 protein kinase 1, SERBP—sterol regulatory element binding protein

Full size image

Melatonin also enhances the antioxidant potential of cells by stimulating the synthesis of enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRd) and augmenting glutathione levels. Melatonin protects, whereas leptin elevates the generation of reactive oxygen species (ROS) (Fig. 3) [67, 68].

Fig. 3
figure 3

Protective effect of Melatonin

Full size image

In healthy animals, the photoperiod is responsible for the significant drop of antioxidant enzymes and it shows opposite effect in the dark in which it increases in circulation. Thus, light affects adversely on healthy animals by decreasing the level of antioxidant and elevates the lipoperoxide level, whereas it shows opposite effect during dark period. It is reported that ROS which is responsible for the disruption of lipid membrane initiates the activation of pro-inflammatory cytokine genes (TNF-α, IL-1, IL-6) by the stimulation of transcription factor NF-kB [69, 70].

The light enters in the brain via a monosynaptic pathway from intrinsically photosensitive retinal ganglion cells in the inner retina to the SCN [71]. In turn, from the SCN the light travels through the multi-synaptic router to the pineal gland. The photoperiodic information circulates from the pineal gland to the organs and regulates day/night cycle [72]. In dark/night, the pineal gland synthesizes melatonin, also known as sleep hormone and improves sleeping tendency. Photoperiodic information travels through the expression of receptors, which synchronously contributes to the circadian rhythm in peripheral tissue and central tissue [73].

Molecular mechanism

In mammals, the molecular mechanism of biological clock is governed by feedback loops of transcriptional–-translational processes (Fig. 2). The primary loop of circadian rhythm consists of two proteins, namely BMAL1 and CLOCK, which stimulate the transcriptional activity of clock control genes—Per1, Per2, Per3 and Cry1, Cry2. After appropriate temporal delay caused by post-translational modifications, these PER and CRY proteins form heterodimer, which enter into the nucleus and prevent their own transcription process through feedback inhibition. The CLOCK and BMAL1 protein interaction inhibit the transcription. The primary loops of these ‘clock genes’ are involved in many interactions between their translated proteins and key biochemical mechanism that regulates intracellular metabolism [23, 74]. In turn, the circadian gene/protein expression is regulated by most of the nuclear factors. It forms a feedback loop and links the biological clock to the cell metabolism. In the peripheral tissue, the rhythmic expression of 50% nuclear receptors is derived from the transcription factors of circadian rhythm protein [23].

Circadian rhythms and its effect on health:

Table 2 shows the effect of circadian rhythm in various metabolic diseases. Circadian clock regulates metabolic rhythms of glucose and lipid metabolism and their disruption could promote diabetes and other related complications [75, 76].

Table 2 Effect of circadian rhythm in associated diseases
Full size table

Diabetes and obesity

The impairment in sugar uptake leads to reduced insulin sensitivity and hyperglycemia [17]. It is feasible that starting from decreased postprandial glucose tolerance at night, the dysregulation of sugar intake may lead to increased use of fatty acid from triglyceride stores in hepatic and adipose tissue [77]. Many human and animal studies revealed that the imbalance absorption between carbohydrate and triglyceride leads to dyslipidaemia and hypertriglyceridemia. This modification in uptake of calorie and its storage decreases the energy balance imposed by sleep debt [78].

Studies have revealed changes in the circadian rhythm between obese and lean subjects. A worldwide study reported that the adverse effect of obesity on biological clock reduces the molecular and physiological rhythm, which largely depends on the target molecule [44]. The routine biological rhythm also exists in the level of many hormones such as adipokine, melatonin and leptin, which follow the circadian clocks that are likely to be driven by endogenous circadian physiology [79, 80]. Early reports indicated that in the obese subjects the concentration of leptin decreased rhythmically, but this work has not been found in recent studies [81]. Furthermore, some endocrine rhythms such as in insulin sensitive obese the circulating melatonin exhibits increased amplitude in obese insulin-sensitive men [82]. At the molecular level, a study in mice reported that obesity reduces clock gene expression, resulting in the alteration in clock gene rhythm or consumption of fatty diet [83, 84]. Obesity is the major factor for developing cardiovascular disease, dyslipidaemia and hypertension [85]. It has recently been reported that changes in daily rhythm in high-fat-diet-induced obese animal model may reject acute effects of the dietary intervention without any long-term changes in energy balance [86]. Only few studies have been reported in humans for routine profile of gene expression in obesity. However, in one of the study using human gluteal subcutaneous fat, there were no differences in gene expression level between lean versus obese individuals [87]. As a part of the strategies proposed for reducing energy intake and for increasing energy output [88], meal intervention at time and frequency could exert a significant influence on weight loss [89,90,91]. Thus, the risk of metabolic syndrome is a major cause by the wrong time sleep/wake and eating.

Neurological disorders

Ageing is a major risk factor for generating the neurological disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and stroke [92]. In each disorder, neuron death and degeneration occur by the involvement of mitochondrial function, oxidative damage, impaired lysosome function and dysregulation of cellular calcium homeostasis [93]. The evidence proved by animal experimental models of various neurological disorders/neurodegenerative diseases, prepared by the intervention of neurotoxins resulting in degeneration of one or many neurons. For example, in PD the animal model was prepared by the induction of MPTP dose, 6-hydroxydopamine and rotenone. These drugs are responsible of neuron degeneration by inhibiting mitochondrial complex I. In the 1990s, studies were initiated to test the general hypothesis that, ageing is the major risk factor for developing neurological disorders; it may be reduced or reversed aging process due to the intermittent fasting (IF). Studies prove that the (IF) protects against these disorders in animal models [94]. A study revealed that when animals are kept on alternate day fasting (ADF) for few months before the intervention of Kainic memory deficit improved [95]. It was also noticed that if mice model kept for few months on ADF acid, the neurons of the hippocampal region are resistant to degeneration and their learning capacity and are resistant to the MPTP, the indication of the improvement in PD model by preventing the degeneration of dopaminergic neurons [96].

Inflammation and immune response

Circadian rhythm disruption causes the metabolic disorders leading to diabetes and obesity, and is also responsible for the alteration in immune system [97]. Immune system plays a key role in the defence mechanism of an organism and maintains the tissue homeostasis. Weak response of immunity causes infection, inflammation and develops autoimmune diseases [98]. Clinical studies revealed that the inflammatory markers have tendency to alter the clock gene expression. In T2DM, the IL6 expression decreases the PER1, CRY1 and BMAL1 expression, whereas this circadian gene shows negative correlation with TNF-α [98, 99]. Central clock controls the metabolism, physiology and temperature of the peripheral clock [100, 101]. Circadian rhythm-associated diseases caused by the inflammation are cardiovascular disease [102], hypertension, chronic kidney disease [103], osteoporosis [104], chronic obstructive pulmonary disease [105], intestinal disease [106], diabetes [107] and obesity [108]. The disrupted circadian clock associated with the peripheral clock generates tissue-specific diseases, mediated by the inflammation (Fig. 4).

Fig. 4
figure 4

Tissue-specific disease developed by the disrupted circadian rhythm mediated by inflammation

Full size image

Conclusions

The circadian system of all organisms contains a core oscillator, away by which this clock can be set by the environment and output behaviours or processes whose phases are determined by the core clock. We conclude that the TRF is the potential intervention on the chronic disrupted circadian rhythm and correlated with the alteration in biological function leading to metabolic syndrome. The therapeutic strategies can be developed and implemented by changing the feeding pattern. There is a need of clinical trial study for a large scale to determine the sustainability and efficacy of TRF intervention. For future prospective, it is important for the clinicians to advice the dietary interventions for the general population. Studies are required using knockout model to understand the exact mechanism of specific gene. Further, the researchers have to develop various studies in combination of in vitro and in vivo experiments.

Availability of data and materials

Not applicable.

Abbreviations

SCN:

Suprachiasmatic nucleus

CHD:

Chronic heart disease

NCBI:

National Center for Biotechnology Information

Per:

Period

Cry:

Cryptochrome

DNMT:

DNA methyltransferase

TET:

Ten–eleven translocase

HAT:

Histone acetyltransferases

HDAC:

Histone deacetylase

TRF:

Time-restricted feeding

HMT:

Histone methyltransferase

HSF:

Heat shock factors

HSP:

Heat shock proteins

MT:

Melatonin transporter

Akt:

Protein kinase B

SOD:

Superoxide dismutase

GPx:

Glutathione peroxidise

GRd:

Glutathione reductase

ROS:

Reactive oxygen species

TNF-α:

Tumour necrosis factor alpha

IL:

Interleukin

cAMP:

Cyclic AMP

S6K1:

S6 protein kinase 1

SERBP:

Sterol regulatory element binding protein

IF:

Intermittent fasting

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

References

  1. Takahashi JS (2017) Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 18:164–179

    CAS  PubMed  Article  Google Scholar 

  2. Balsalobre A, Brown SA, Marcacci L, Tronche F, Kellendonk C, Reichardt CH, Schütz G et al (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289(5488):2344–2347

    CAS  PubMed  Article  Google Scholar 

  3. Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M et al (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288(5466):682–685

    CAS  PubMed  Article  Google Scholar 

  4. Abe M, Herzog ED, Yamazaki S, Straume M, Tei H, Sakaki Y et al (2002) Circadian rhythms in isolated brain regions. J Neuro 22:350–356

    CAS  Article  Google Scholar 

  5. Jin XW, Shearman LP, Weaver DR, Zylka MJ, De Vries GJ, Reppert SM (1999) A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell 96:57–68

    CAS  PubMed  Article  Google Scholar 

  6. Gill S, Panda SA (2015) Smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits. Cell Metab 22:789–798

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. Chow LS, Manoogian ENC, Alvear A, Fleischer JG, Thor H, Dietsche K et al (2020) Time-restricted eating effects on body composition and metabolic measures in humans who are overweight: a feasibility study. Obesity 28:860–869

    CAS  PubMed  Article  Google Scholar 

  8. Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA (2013) Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring) 21:1370–1379

    CAS  Article  Google Scholar 

  9. Halberg N, Henriksen M, Soderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F (2005) Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985) 99:2128–2136

    CAS  Article  Google Scholar 

  10. Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, Pearson M, Nassar M, Telljohann R, Maudsley S et al (2007) Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 42:665–674

    CAS  PubMed  Article  Google Scholar 

  11. Jiang P, Turek FW (2017) Timing of meals: when is as critical as what and how much. Am J Physiol Endocrinol Metab 312:E369-380

    PubMed  PubMed Central  Article  Google Scholar 

  12. Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466:627–631

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Paschos GK, Ibrahim S, Song WL, Kunieda T, Grant G, Reyes TM et al (2012) Obesity in mice with adipocyte-specific deletion of clock component Arntl. Nat Med 18:1768–1777

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Green CB, Takahashi JS, Bass J (2008) The meter of metabolism. Cell 134:728–742

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Zimmet PZ, Magliano DJ, Herman WH, Shaw JE (2014) Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol 2:56–64

    PubMed  Article  Google Scholar 

  16. Le Martelot G, Canella D, Symul L, Migliavacca E, Gilardi F, Liechti R et al (2012) Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles. PLoS Biol 10:e1001442

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  17. Ruger M, Scheer F (2009) Effects of circadian disruption on the cardiometabolic system. Rev Endocr Metab Disord 10:245–260

    PubMed  PubMed Central  Article  Google Scholar 

  18. Rudic RD, McNamara P, Curtis AM, Boston RC, Panda S, Hogenesch JB et al (2004) BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol 2:e377

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  19. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E et al (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308:1043–1045

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Bass J (2012) Circadian topology of metabolism. Nature 491:348–356

    CAS  PubMed  Article  Google Scholar 

  21. Woon PY, Kaisaki PJ, Braganc AJ, Bihoreau MT, Levy JC, Farrall M et al (2007) Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc Natl Acad Sci USA 104:14412–14417

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Scott EM, Carter AM, Grant PJ (2008) Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes (Lond) 32:658–662

    CAS  Article  Google Scholar 

  23. Ye R, Selby CP, Chiou YY, Ozkan-Dagliyan I, Gaddameedhi S, Sancar A (2014) Dual modes of CLOCK: BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock. Genes Dev 28(18):1989–1998

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Chiou YY, Yang Y, Rashid N, Ye R, Selby CP, Sancar A (2016) Mammalian Period represses and derepresses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner. Proc Natl Acad Sci USA 113(41):E6072–E6079

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. Guillaumond F, Dardente H, Giguere V, Cermakian N (2005) Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J Biol Rhythms 20:391–403

    CAS  PubMed  Article  Google Scholar 

  26. Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U et al (2002) The orphan nuclear receptor REV-ERB alpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110:251–260

    CAS  PubMed  Article  Google Scholar 

  27. Panda S, Hogenesch JB, Kay SA (2002) Circadian rhythms from flies to human. Nature 417(6886):329–335

    CAS  PubMed  Article  Google Scholar 

  28. Zhang HM, Zhang Y (2014) Melatonin: a well-documented antioxidant with conditional pro-oxidant actions. J Pineal Res 57(2):131–146

    CAS  PubMed  Article  Google Scholar 

  29. Ripperger JA, Schibler U (2006) Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions. Nat Genet 38(3):369–374

    CAS  PubMed  Article  Google Scholar 

  30. Menet JS, Rodriguez J, Abruzzi KC, Rosbash M (2012) Nascent-seq reveals novel features of mouse circadian transcriptional regulation. Elife 1:e00011

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  31. Lande-Diner L, Boyault C, Kim JY, Weitz CJ (2013) A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery. Proc Natl Acad Sci USA 110:16021–16026

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Trott AJ, Menet JS (2018) Regulation of circadian clock transcriptional output by CLOCK: BMAL1. PLoSGenet 14:e1007156

    Google Scholar 

  33. Allis CD, Jenuwein T, Reinberg D (2016) Overview and concepts. Cold Spring Harb Perspect Biol 8:a019372

    Article  CAS  Google Scholar 

  34. Moore EM, Mander AG, Ames D, Kotowicz MA, Carne RP, Brodaty H et al (2013) Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care 36:2981–2987

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. Ito S, D’Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y (2010) Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466:1129–1133

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. Verdone L, Agricola E, Caserta M, Mauro ED (2006) Histone acetylation in gene regulation. Brief Funct Genom 5(3):209–221

    CAS  Article  Google Scholar 

  37. Zhang Y, Kutateladze TG (2018) Diet and the epigenome. Nat Commun 9:3375

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  38. Vinoth A, Thirunalasundari T, Shanmugam M, Uthrakumar A, Suji S, Rajkumar U (2018) Evaluation of DNA methylation and mRNA expression of heat shock proteins in thermal manipulated Chicken. Cell Stress Chaperones 23:235–252

    CAS  PubMed  Article  Google Scholar 

  39. Yan XP, Liu HH, Liu JY, Zhang RP, Wang GS, Li QQ et al (2015) Evidence in duck for supporting alteration of incubation temperature may have influence on methylation of genomic DNA. Poult Sci 94:2537–2545

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. Alvarado S, Fernald RD, Storey KB, Szyf M (2014) The dynamic nature of DNA methylation: a role in response to social and seasonal variation. Integr Comp Biol 54(1):68–76

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. Bentz AB, Sirman AE, Wada H, Navara KJ, Hood WR (2016) Relationship between maternal environment and DNA methylation patterns of estrogen receptor alpha in wild Eastern Bluebird (Sialia sialis) nestlings: a pilot study. Ecol Evol 6:4741–4752

    PubMed  PubMed Central  Article  Google Scholar 

  42. Gómez JL, Gómez OFM, García MV, Molina VR, Dávalos LC, Ávila VA et al (2016) Anticonvulsant effect of time-restricted feeding in a pilocarpine-induced seizure model: metabolic and epigenetic implications. Front Cell Neurosci 10:7

    Google Scholar 

  43. Johnston JD (2014) Physiological responses to food intake throughout the day. Nutr Res Rev 27:107–118

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Sherman GD, Lee JJ, Cuddy AJ, Renshon J, Oveis C, Gross JJ et al (2012) Leadership is associated with lower levels of stress. Proc Natl Acad Sci USA 109:17903–17907

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Chaix A, Zarrinpar A, Miu P, Panda S (2014) Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab 20:991–1005

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. Belkacemi L, Jelks A, Che CH, Ross MG, Desai M (2011) Altered placental development in undernourished rats: role of maternal glucocorticoids. Reprod Biol Endocrinol 9:105

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S et al (2012) Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15:848–860

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. Cauter VE, Polonsky KS, Scheen AJ (1997) Roles of circadian rhythmicity and sleep in human glucose regulation. Endocr Rev 18:716–738

    PubMed  Google Scholar 

  49. Morgan L, Hampton S, Gibbs M, Arendt J (2003) Circadian aspects of postprandial metabolism. Chronobiol Int 20(5):795–808

    CAS  PubMed  Article  Google Scholar 

  50. Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14:2950–2961

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. Refinetti R, Kaufman CM, Menaker M (1994) Complete suprachiasmatic lesions eliminate circadian rhythmicity of body temperature and locomotor activity in golden hamsters. J Comp Physiol A 175:223–232

    CAS  PubMed  Article  Google Scholar 

  52. Morimoto R (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–3796

    CAS  PubMed  Article  Google Scholar 

  53. Sarge KD, Murphy SP, Morimoto RI (1993) Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. Mol Cell Biol 13:1392–1407

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Kornmann B, Schaad O, Bujard H, Takahashi JS, Schibler U (2007) System-driven and oscillator dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol 5:e34

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  55. Reinke H, Saini C, Fleury-Olela F, Dibner C, Benjamin IJ, Schibler U (2008) Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor. Genes Dev 22:331–345

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. Pandi-Perumal SR, Verster JC, Kayumov L et al (2006) Sleep disorders, sleepiness and traffic safety: a public health menance. Braz J Med Biol Res 39:863–871

    CAS  PubMed  Article  Google Scholar 

  57. Dubocovich ML (2007) Melatonin receptors: role on sleep and circadian rhythm regulation. Sleep Med 8:34–42

    PubMed  Article  Google Scholar 

  58. Kalsbeek A, Fliers E, Romijn JA, La Fleur SE, Wortel J et al (2001) The suprachiasmatic nucleus generates the diurnal changes in plasma leptin levels. Endocrinology 142:2677–2685

    CAS  PubMed  Article  Google Scholar 

  59. Licinio J, Negrão AB, Mantzoros C, Kaklamani V, Wong ML, Bongiorno PB et al (1998) Synchronicity of frequently sampled, 24 hour concentrations of circulating leptin, luteinizing hormone and estradiol in healthy women. Proc Nat Acad Sci 95:2541–2546

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. Wolden-Hanson T, Mitton DR, McCants RL, Yellon SM, Wilkinson CW, Matsumoto AM et al (2000) Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology 141:487–497

    CAS  PubMed  Article  Google Scholar 

  61. Rasmussen M, Müller HP, Björck L (1999) Protein GRAB of Streptococcus pyogenes regulates proteolysis at the bacterial cell surface by binding α2-macroglobulin. J Biol Chem 274:15336–15344

    CAS  PubMed  Article  Google Scholar 

  62. Cardozo AK, Ortis F, Storling J et al (2005) Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells. Diabetes 54:452–461

    CAS  PubMed  Article  Google Scholar 

  63. Ekmecioglu C (2006) Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother 60:97–108

    Article  CAS  Google Scholar 

  64. Dubocovich ML, Delagrange P, Kraused ND, Sugden D, Cardinali DP, Olcese J (2010) International Union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev 62:343–380

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. Bazwinsky-Wutschke I, Bieseke L, Muhlbauer E, Peschke E (2014) Influence of melatonin receptor signalling on parameters involved in blood glucose regulation. J Pineal Res 56:82–96

    CAS  PubMed  Article  Google Scholar 

  66. Reiter RJ, Garcia JJ, Pie J (1998) Oxidative toxicity in models of neurodegeneration: responses to melatonin. Restor Neurol Neurosci 12:135–142

    CAS  PubMed  Google Scholar 

  67. Yamagishi T (2001) Trust as a form of social intelligence. In: Cook KS (ed) Trust in society. Russell Sage, New York, pp 121–147

    Google Scholar 

  68. Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM (2000) The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. Toxicology 143:219–226

    CAS  PubMed  Article  Google Scholar 

  69. Schreck R, Baeuerle PA (1991) A role for oxygen radicals as second messengers. Trends Cell Biol 1(2–3):39–42

    CAS  PubMed  Article  Google Scholar 

  70. Berson DM, Dunn FA, Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science 295:1070–1073

    CAS  PubMed  Article  Google Scholar 

  71. Moore RY (1996) Neural control of the pineal gland. Behav Brain Res 73(1–2):125–130

    CAS  PubMed  Google Scholar 

  72. Zawilska JB, Skene DJ, Arendt J (2009) Physiology and pharmacology of melatonin. Pharmacol Rep 61(3):383–410

    CAS  PubMed  Article  Google Scholar 

  73. Buhr ED, Takahashi JS (2013) Molecular components of the mammalian circadian clock. Handb Exp Pharmacol 217:3–27

    CAS  Article  Google Scholar 

  74. Panda S, Antoch MP, Miller BH et al (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109:307–320

    CAS  PubMed  Article  Google Scholar 

  75. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941

    CAS  PubMed  Article  Google Scholar 

  76. Lund J, Arendt J, Hampton SM, English J, Morgan LM (2001) Postprandial hormone and metabolic responses amongst shift workers in Antarctica. J Endocrinol 171(3):557–564

    CAS  PubMed  Article  Google Scholar 

  77. Scheer FA, Hilton MF, Mantzoros CS, Shea SA (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 106(11):4453–4458

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. Shea SA, Hilton MF, Orlova C, Ayers RT, Mantzoros CS (2005) Independent circadian and sleep/wake regulation of adipokines and glucose in humans. J Clin Endocrinol Metab 90:2537–2544

    CAS  PubMed  Article  Google Scholar 

  79. Otway DT, Frost G, Johnston JD (2009) Circadian rhythmicity in murine pre-adipocyte and adipocyte cells. Chronobiol Int 26:1340–1354

    CAS  PubMed  Article  Google Scholar 

  80. Sinha MK, Ohannesian JP, Heiman ML et al (1996) Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Investig 97:1344–1347

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. Mantele S, Otway DT, Middleton B, Bretschneider S, Wright J, Robertson MD et al (2012) Daily rhythms of plasma melatonin, but not plasma leptin or leptin mRNA, vary between lean, obese and type 2 diabetic men. PLoS ONE 7:e37123

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. Ando H, Yanagihara H, Hayashi Y, Obi Y, Tsuruoka S, Takamura T et al (2005) Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 146:5631–5636

    CAS  PubMed  Article  Google Scholar 

  83. Kohsaka A, Laposky AD, Ramsey KM, Estrada C, Joshu C, Kobayashi Y et al (2007) High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab 6:414–421

    CAS  PubMed  Article  Google Scholar 

  84. Lavie CJ, Milani RV (2003) Obesity and cardiovascular disease: The Hippocrates paradox? J Am Coll Cardiol 42:677–679

    PubMed  Article  Google Scholar 

  85. Eckel-Mahan KL, Patel VR, de Mateo S, Orozco-Solis R, Ceglia NJ, Sahar S et al (2003) Reprogramming of the circadian clock by nutritional challenge. Cell 155:1464–1478

    Article  CAS  Google Scholar 

  86. Otway DT, Mantele S, Bretschneider S, Wright J, Trayhurn P, Skene DJ, Robertson MD, Johnston JD (2011) Rhythmic diurnal gene expression in human adipose tissue from individuals who are lean, overweight, and type 2 diabetic. Diabetes 60:1577–1581

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. Thompson WG, Cook DA, Clark MM, Bardia A, Levine JA (2007) Treatment of obesity. Mayo Clin Proc 82:93–101

    PubMed  Article  Google Scholar 

  88. Paoli A, Moro T, Marcolin G, Neri M, Bianco A, Palma A, Grimaldi K (2021) High-intensity interval resistance training (hirt) influences resting energy expenditure and respiratory ratio in non-dieting individuals. J Transl Med 10:237

    Article  Google Scholar 

  89. Garaulet M, Gomez-Abellan P (2014) Timing of food intake and obesity: a novel association. Physiol Behav 134:44–50

    CAS  PubMed  Article  Google Scholar 

  90. Kulovitz MG, Kravitz LR, Mermier C, Gibson AL, Conn CA, Kolkmeyer D, Kerksick CM (2014) Potential role of meal frequency as a strategy for weight loss and health in overweight or obese adults. Nutrition 30:386–392

    PubMed  Article  Google Scholar 

  91. Yankner BA, Lu T, Loerch P (2008) The aging brain. Annu Rev Pathol 3:41–66

    CAS  PubMed  Article  Google Scholar 

  92. Mattson MP (2003) Excitotoxic and excitoprotective mechanisms: abundant targets for the prevention and treatment of neurodegenerative disorders. Neuromol Med 3:65–94

    CAS  Article  Google Scholar 

  93. Mattson MP (2012) Evolutionary aspects of human exercise–born to run purposefully. Ageing Res Rev 11:347–352

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  94. Bruce-Kelle AJ, Umberger G, McFall R, Mattson MP (1999) Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann Neurol 45:8–15

    Article  Google Scholar 

  95. Duan W, Mattson MP (1999) Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson’s disease. J Neurosci Res 57:195–206

    CAS  PubMed  Article  Google Scholar 

  96. Hood, Amir S (2017) The aging clock: circadian rhythms and later life. J Clin Investig 127:437

    PubMed  PubMed Central  Article  Google Scholar 

  97. Reale M, Conti L, Velluto D (2018) Immune and inflammatory-mediated disorders: from bench to bedside. J Immunol Res 7197931:3

    Google Scholar 

  98. Wang YS, Pati P, Xu YM, Chen F, Stepp DW, Huo YQ et al (2016) Endotoxin disrupts circadian rhythms in macrophages via reactive oxygen species. PLoS ONE 2016:11

    Google Scholar 

  99. Haimovich B, Calvano J, Haimovich AD, Calvano SE, Coyle SM, Lowry SF (2010) In vivo endotoxin synchronizes and suppresses clock gene expression in human peripheral blood leukocytes. Crit Care Med 38:751–758

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  100. Dibner C, Schibler U, Albrecht U (2010) The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 72:517–549

    CAS  PubMed  Article  Google Scholar 

  101. Saini C, Morf J, Stratmann M, Gos P, Schibler U (2012) Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators. Genes Dev 26:567–580

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. Nska PA, Formanowicz D (2020) Chronic kidney disease as oxidative stress- and inflammatory-mediated cardiovascular disease. Antioxidants 9:752

    Article  CAS  Google Scholar 

  103. Mihai S, Codrici E, Popescu ID, Enciu AM, Albulescu L, Necula LG, Mambet C, Anton G, Tanase C (2018) Inflammation related mechanisms in chronic kidney disease prediction, progression, and outcome. J Immunol. https://doi.org/10.1155/2018/2180373

    Article  Google Scholar 

  104. Tanaka Y (2019) Clinical immunity in bone and joints. J Bone Miner Metab 37:2–8

    CAS  PubMed  Article  Google Scholar 

  105. Barnes PJ (2019) Inflammatory endotypes in COPD. Allergy 1:1249–1256

    Google Scholar 

  106. Sommer F, Backhed F (2013) The gut microbiota–masters of host development and physiology. Nat Rev Microbiol 11:227–238

    CAS  PubMed  Article  Google Scholar 

  107. Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Investig 116:1793–1801

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  108. Monteiro R (2009) Chronic inflammation in the metabolic syndrome: emphasis on adipose tissue. In: Soares R, Costa C (eds) Oxidative stress, inflammation and angiogenesis in the metabolic syndrome. Springer, New York, pp 65–83

    Chapter  Google Scholar 

  109. Yokomori N, Tawata M, Onaya T (1999) DNA demethylation during the differentiation of 3T3–L1 cells affects the expression of the mouse GLUT4 gene. Diabetes 48:685–690

    CAS  PubMed  Article  Google Scholar 

  110. Bouchard L, Hivert MF, Guay SP, St-Pierre J, Perron P, Brisson D (2012) Placental adiponectin gene DNA methylation levels are associated with mothers’ blood glucose concentration. Diabetes 61:1272–1280

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  111. Kuroda A, Rauch TA, Todorov I, Ku HT, Al-Abdullah IH, Kandeel F et al (2009) Insulin gene expression is regulated by DNA methylation. PLoS ONE 4:e6953

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  112. Bollati V, Baccarelli A, Sartori S, Tarantini L, Motta V, Rota F et al (2010) Epigenetic effects of shiftwork on blood DNA methylation. Chronobiol Int 27:1093–1104

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  113. Hermsdorff HH, Mansego ML, Campión J, Milagro FI, Zulet MA, Martínez JA (2013) TNF-alpha promoter methylation in peripheral white blood cells: relationship with circulating TNFa, truncal fat and n-6 PUFA intake in young women. Cytokine 64:265–271

    CAS  PubMed  Article  Google Scholar 

  114. Lomba A, Martinez JA, Garcia-Diaz DF, Paternain L, Marti A, Campion J et al (2010) Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FAS and NDUFB6 gene promoters. Mol Genet Metab 101:273–278

    CAS  PubMed  Article  Google Scholar 

  115. Lillycrop KA, Phillips ES, Torrens C, Hanson MA, Jackson AA, Burdge GC (2008) Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring. Br J Nutr 100:278–282

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  116. Zheng S, Rollet M, Pan YX (2011) Maternal protein restriction during pregnancy induces CCAAT/enhancer-binding protein (C/EBPb) expression through the regulation of histone modification at its promoter region in female offspring rat skeletal muscle. Epigenetics 6:161–170

    CAS  PubMed  Article  Google Scholar 

  117. Uriarte G, Paternain L, Milagro FI, Martínez JA, Campion J (2013) Shifting to a control diet after a high-fat, high-sucrose diet intake induces epigenetic changes in retroperitoneal adipocytes of Wistar rats. J Physiol Biochem 69:601–611

    CAS  PubMed  Article  Google Scholar 

  118. Widiker S, Karst S, Wagener A, Brockmann GA (2010) High-fat diet leads to a decreased methylation of the Mc4r gene in the obese BFMI and the lean B6 mouse lines. J Appl Genet 51:193–197

    CAS  PubMed  Article  Google Scholar 

  119. Crujeiras AB, Campion J, Díaz-Lagares A, Milagro FI, Goyenechea E, Abete I et al (2013) Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: a translational study. Regul Pept 186:1–6

    CAS  PubMed  Article  Google Scholar 

  120. Nikolaeva S, Pradervand S, Centeno G, Zavadova V, Tokonami N, Maillard M et al (2012) The circadian clock modulates renal sodium handling. J Am Soc Nephrol 23:1019–1026

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  121. Zuber AM, Centeno G, Pradervand S, Nikolaeva S, Maquelin L, Cardinaux L et al (2009) Molecular clock is involved in predictive circadian adjustment of renal function. Proc Natl Acad Sci USA 106:16523–16528

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  122. Stow LR, Richards J, Cheng KY, Lynch IJ, Jeffers LA, Greenlee MM et al (2012) The circadian protein period 1 contributes to blood pressure control and coordinately regulates renal sodium transport genes. Hypertension 59:1151–1156

    CAS  PubMed  Article  Google Scholar 

  123. Doi M, Takahashi Y, Komatsu R, Yamazaki F, Yamada H, Haraguchi S et al (2010) Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6. Nat Med 16:67–74

    CAS  PubMed  Article  Google Scholar 

  124. Curtis AM, Cheng Y, Kapoor S, Reilly D, Price TS, Fitzgerald GA (2007) Circadian variation of blood pressure and the vascular response to asynchronous stress. Proc Natl Acad Sci USA 104:3450–3455

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  125. Dallmann R, Weaver DR (2010) Altered body mass regulation in male mPeriod mutant mice on high-fat diet. Chronobiol Int 27:1317–1328

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  126. Guo B, Chatterjee S, Li L, Kim JM, Lee J, Yechoor VK et al (2012) The clock gene, brain and muscle Arnt-like 1, regulates adipogenesis via Wnt signaling pathway. FASEB J 26:3453–3463

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  127. Delezie J, Dumont S, Dardente H, Oudart H, Grechez-Cassiau A, Klosen P et al (2012) The nuclear receptor REV-ERBalpha is required for the daily balance of carbohydrate and lipid metabolism. FASEB J 26:3321–3335

    CAS  PubMed  Article  Google Scholar 

  128. Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T et al (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 485:62–68

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  129. Pappa KI, Gazouli M, Anastasiou E, Iliodromiti Z, Antsaklis A, Anagnou NP (2012) The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus. Diabetes Res Clin Pract 99:151–157

    PubMed  Article  CAS  Google Scholar 

  130. Lee J, Kim MS, Li R, Liu VY, Fu L, Moore DD et al (2011) Loss of Bmal1 leads to uncoupling and impaired glucose-stimulated insulin secretion in beta-cells. Islets 3:381–388

    PubMed  PubMed Central  Article  Google Scholar 

  131. Peschke E, Muhlbauer E (2010) New evidence for a role of melatonin in glucose regulation. Best Pract Res Clin Endocrinol Metab 24:829–841

    CAS  PubMed  Article  Google Scholar 

  132. Reddy TE, Gertz J, Crawford GE, Garabedian MJ, Myers RM (2012) The hypersensitive glucocorticoid response specifically regulates period 1 and expression of circadian genes. Mol Cell Biol 32:3756–3767

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  133. Christ E, Pfeffer M, Korf HW, von Gall C (2010) Pineal melatonin synthesis is altered in Period1 deficient mice. Neuroscience 171:398–406

    CAS  PubMed  Article  Google Scholar 

  134. Jung-Hynes B, Huang W, Reiter RJ, Ahmad N (2010) Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells. J Pineal Res 49:60–68

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Silver AC, Arjona A, Walker WE, Fikrig E (2012) The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity. Immunity 36:251–261

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  136. Narasimamurthy R, Hatori M, Nayak SK, Liu F, Panda S, Verma IM (2012) Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. Proc Natl Acad Sci USA 109:12662–12667

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. Ratajczak CK, Boehle KL, Muglia LJ (2009) Impaired steroidogenesis and implantation failure in Bmal1-/- mice. Endocrinology 150:1879–1885

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  138. Chappell PE, White RS, Mellon PL (2003) Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1–7 cell line. J Neurosci 23:11202–11213

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  139. Wilkinson MJ, Manoogian ENC, Zadourian A et al (2020) Tenhour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome. Cell Metab 31(1):92–104

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgements

We are thankful to Indian Council of Medical Research (ICMR), New Delhi, for providing us with this project fund.

Funding

The fund for this project is sanctioned by ICMR, New Delhi, with Ref No. 45/13/2019-HUM/BMS.

Author information

Authors and Affiliations

  1. Department of Biochemistry, King George’s Medical University, Lucknow, Uttar Pradesh, India

    Nazmin Fatima & Gyanendra Kumar Sonkar

  2. Department of Biosciences, Integral University, Lucknow, India

    Sangeeta Singh

Authors
  1. Nazmin Fatima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gyanendra Kumar Sonkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sangeeta Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors were involved in conception and design of the work. NF, GKS, SS performed screening and selection of articles. NF drafted the manuscript. All authors were involved in editing and revision of the manuscript and final approval of the version submitted for publication. All authors agree to be accountable for all aspects of the work and in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gyanendra Kumar Sonkar.

Ethics declarations

Ethics approval and consent to participate

This review article which is submitted here as part of project was approved by the ethical committee of the institution with reference no. 123/IAEC/2019.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fatima, N., Sonkar, G.K. & Singh, S. Circadian mechanism disruption is associated with dysregulation of inflammatory and immune responses: a systematic review. Beni-Suef Univ J Basic Appl Sci 11, 107 (2022). https://doi.org/10.1186/s43088-022-00290-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s43088-022-00290-4

Keywords

  • Circadian rhythm
  • Suprachiasmatic nuclei
  • Central clock
  • Peripheral clock
  • Time-restricted feeding
  • Metabolism