Eat, Train, Sleep—Retreat? Hormonal Interactions of Intermittent Fasting, Exercise and Circadian Rhythm

The circadian rhythmicity of endogenous metabolic and hormonal processes is controlled by a complex system of central and peripheral pacemakers, influenced by exogenous factors like light/dark-cycles, nutrition and exercise timing. There is evidence that alterations in this system may be involved in the pathogenesis of metabolic diseases. It has been shown that disruptions to normal diurnal rhythms lead to drastic changes in circadian processes, as often seen in modern society due to excessive exposure to unnatural light sources. Out of that, research has focused on time-restricted feeding and exercise, as both seem to be able to reset disruptions in circadian pacemakers. Based on these results and personal physical goals, optimal time periods for food intake and exercise have been identified. This review shows that appropriate nutrition and exercise timing are powerful tools to support, rather than not disturb, the circadian rhythm and potentially contribute to the prevention of metabolic diseases. Nevertheless, both lifestyle interventions are unable to address the real issue: the misalignment of our biological with our social time.

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Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome

Frontiers in Physiology ◽

10.3389/fphys.2021.641461 ◽

2021 ◽

Vol 12 ◽

Author(s):

Antonino Mulè ◽

Eleonora Bruno ◽

Patrizia Pasanisi ◽

Letizia Galasso ◽

Lucia Castelli ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Circadian Rhythm ◽

Metabolic Diseases ◽

Activity Level ◽

Activity Count ◽

Cross Sectional ◽

The Metabolic Syndrome ◽

Parametric Analyses ◽

Rest Activity

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person’s circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

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Attenuation of myocardial injury in mice with functional deletion of the circadian rhythm gene mPer2

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01280.2008 ◽

2010 ◽

Vol 298 (3) ◽

pp. H1088-H1095 ◽

Cited By ~ 28

Author(s):

Jitka A. I. Virag ◽

Jessica L. Dries ◽

Peter R. Easton ◽

Amy M. Friesland ◽

Jon H. DeAntonio ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Circadian Rhythm ◽

Contractile Function ◽

Myocardial Infarct ◽

Inflammatory Cells ◽

Diurnal Rhythms ◽

Cardiomyocyte Hypertrophy ◽

Wild Type ◽

Infarct Zone

Variations in circadian rhythms are evident in the incidence of cardiovascular disease, and the risk of cardiovascular events increases when rhythms are disrupted. The suprachiasmatic nucleus is the central circadian pacemaker that regulates the daily rhythm of peripheral organs. Diurnal rhythms have more recently been shown to exist in myocardial tissue and are involved in metabolism and contractile function. Thus we sought to determine whether the functional deletion of the circadian rhythm mouse periodic gene 2 (mPer2) would protect the heart against ischemic injury. Nonreperfused myocardial infarction was induced in anesthetized, ventilated C57 ( n = 17) and mPer2 mutant (mPer2-M; n = 15) mice via permanent ligation of the left anterior descending coronary artery. At 4 days post-myocardial infarction, we observed a 43% reduction of infarct area in mPer2-M mice compared with wild-type mice. This is coincident with 25% less macrophage infiltration, 43% higher capillary density, 17% increase in hypertrophy, and 15% less cardiomyocyte apoptosis in the infarct zone. Also, matrix metalloproteinase-9 was expressed in inflammatory cells in both groups, but total protein was 40% higher in wild-type mice, whereas it was not elevated in mPer2-M mice in response to injury. The functional deletion of the mPer2 gene reduces the severity of myocardial infarct injury by limiting the inflammatory response, reducing apoptosis, and inducing cardiomyocyte hypertrophy, thus preserving cardiac function. These findings collectively imply that the disruption of the circadian clock gene mPer2 is protective. Understanding the interactions between circadian rhythm genes and cardiovascular disease may provide insights into potential preventative and therapeutic strategies for susceptible populations.

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Abstract P160: Non-invasive Method to Assess Human Circadian Rhythms

Hypertension ◽

10.1161/hyp.68.suppl_1.p160 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Daian Chen ◽

S Justin Thomas ◽

David A Calhoun ◽

David M Pollock ◽

Jennifer S Pollock

Keyword(s):

Circadian Rhythm ◽

Circadian Rhythms ◽

Salivary Cortisol ◽

Metabolic Diseases ◽

Clock Genes ◽

Light Exposure ◽

Rna Isolation ◽

Buccal Cells ◽

Non Invasive ◽

Salivary Melatonin

Circadian rhythms are controlled by an endogenous time-keeping system oscillating approximately on a 24-h cycle under constant conditions. These rhythms depend on a network of interacting genes and proteins, including transcriptional activators such as CLOCK, NPAS2, and ARNTL (BMAL1), which induce transcription of the clock genes Period ( Per1 , Per2 , and Per3 ) and Cryptochrome ( Cry1 and Cry2 ). Human salivary cortisol and melatonin follow a clear circadian rhythm as well. Disruption of the circadian rhythm and sleep-wake cycles are considered risk factors for a variety of health problems, especially hypertension and other cardiovascular and metabolic diseases. Here we put together practical methods for assessing circadian rhythms in adult subjects conducted by each individual. This method is non-invasive, inexpensive and provides a predictive profile of an individual’s circadian rhythm related to clock-controlled gene expression in buccal cells, salivary cortisol, salivary melatonin, and subject’s activity or sleep. Subjects are instructed on how to obtain buccal cells using swabs (Whatman OmniSwab) from the inside of their cheeks and collect saliva using salivettes (Sarstedt) every 4 hours starting at 6am, for 2 consecutive days. Subjects also wear actigraphy watches (Phillips Respironics) during the 2 days, to record their activity, light exposure and estimates of sleep times. To monitor adherence to correct time point collections, each subject is given an electronic vial called eCAP (Information Mediary Corp) that records the exact time the container is opened to place samples once collected. We demonstrate feasibility to extract up to 150ng/μl of RNA (Ambion RNAqueous-Micro Total RNA Isolation Kit) from buccal cells swabs. Salivary melatonin and cortisol are measured by radioimmunoassay (Buhlmann Lab) with melatonin peak levels ranging from 14 to 23 pg/ml and cortisol peak levels ranging from 10 to 24 ng/ml. We suggest that buccal cell expression of clock-controlled genes, salivary melatonin, salivary cortisol, and actigraphy data are valuable in providing reliable assessment of human circadian rhythm profiles under a variety of conditions.

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Circadian Rhythms and Homeostatic Mechanisms for Sleep Regulation

Integrative Sleep Medicine ◽

10.1093/med/9780190885403.003.0005 ◽

2021 ◽

pp. 65-86

Author(s):

Cassie J. Hilditch ◽

Erin E. Flynn-Evans

Keyword(s):

Circadian Rhythm ◽

Circadian Rhythms ◽

Process Model ◽

Modern Society ◽

Current Evidence ◽

Sleep Regulation ◽

Sleep Homeostasis ◽

Short And Long Term ◽

Homeostatic Mechanisms

This chapter examines circadian rhythms and homeostatic mechanisms for sleep regulation. It reviews the current evidence describing the two-process model of sleep regulation and how to assess disruption to either of these sleep drives. This chapter also reviews the role of the photic and non-photic resetting of the circadian rhythm and describes how some aspects of modern society can cause sleep and circadian disruption. Further, this chapter describes how misalignment between the circadian rhythm and sleep homeostasis, such as occurs during jet lag and shift-work, can lead to sleep disruption. The short- and long-term consequences of circadian misalignment are also reviewed.

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“Gut Microbiota-Circadian Clock Axis” in Deciphering the Mechanism Linking Early-Life Nutritional Environment and Abnormal Glucose Metabolism

International Journal of Endocrinology ◽

10.1155/2019/5893028 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Liyuan Zhou ◽

Lin Kang ◽

Xinhua Xiao ◽

Lijing Jia ◽

Qian Zhang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Circadian Rhythm ◽

Gut Microbiota ◽

Circadian Clock ◽

Early Life ◽

Metabolic Diseases ◽

Clock Genes ◽

Early Stage ◽

Adult Life ◽

Metabolic Memory

The prevalence of diabetes mellitus (DM) has been increasing dramatically worldwide, but the pathogenesis is still unknown. A growing amount of evidence suggests that an abnormal developmental environment in early life increases the risk of developing metabolic diseases in adult life, which is referred to as the “metabolic memory” and the Developmental Origins of Health and Disease (DOHaD) hypothesis. The mechanism of “metabolic memory” has become a hot topic in the field of DM worldwide and could be a key to understanding the pathogenesis of DM. In recent years, several large cohort studies have shown that shift workers have a higher risk of developing type 2 diabetes mellitus (T2DM) and worse control of blood glucose levels. Furthermore, a maternal high-fat diet could lead to metabolic disorders and abnormal expression of clock genes and clock-controlled genes in offspring. Thus, disorders of circadian rhythm might play a pivotal role in glucose metabolic disturbances, especially in terms of early adverse nutritional environments and the development of metabolic diseases in later life. In addition, as a peripheral clock, the gut microbiota has its own circadian rhythm that fluctuates with periodic feeding and has been widely recognized for its significant role in metabolism. In light of the important roles of the gut microbiota and circadian clock in metabolic health and their interconnected regulatory relationship, we propose that the “gut microbiota-circadian clock axis” might be a novel and crucial mechanism to decipher “metabolic memory.” The “gut microbiota-circadian clock axis” is expected to facilitate the future development of a novel target for the prevention and intervention of diabetes during the early stage of life.

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Intermittent Fasting: Physiological Implications on Outcomes in Mice and Men

Physiology ◽

10.1152/physiol.00030.2019 ◽

2020 ◽

Vol 35 (3) ◽

pp. 185-195 ◽

Cited By ~ 2

Author(s):

Ju Hee Lee ◽

Navkiran Verma ◽

Nikita Thakkar ◽

Christy Yeung ◽

Hoon-Ki Sung

Keyword(s):

Animal Studies ◽

Metabolic Diseases ◽

Intermittent Fasting ◽

Systemic Effects ◽

Clinical Settings ◽

Dietary Interventions ◽

Positive Health ◽

Underlying Mechanisms ◽

Preclinical And Clinical Studies ◽

Insight Into

Intermittent fasting (IF) is a widely practiced dietary method that encompasses periodic restriction of food consumption. Due to its protective benefits against metabolic diseases, aging, and cardiovascular and neurodegenerative diseases, IF continues to gain attention as a preventative and therapeutic intervention to counteract these chronic diseases. Although numerous animal studies have reported positive health benefits of IF, its feasibility and efficacy in clinical settings remain controversial. Importantly, since dietary interventions such as IF have systemic effects, thoroughly investigating the tissue-specific changes in animal models is crucial to identify IF’s mechanism and evaluate its potential adverse effects in humans. As such, we will review and compare the outcomes and underlying mechanisms of IF in both animal and human studies. Moreover, the limitations of IF and inconsistencies between preclinical and clinical studies will be discussed to provide insight into the gaps between translating research from bench to bedside.

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Modulation of Anti-Oxidant, Anti-Inflammatory and Metabolism-Controlling Genes Expressions by Ramadan Intermittent Fasting: A Prospective Observational Study

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_023 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1265-1265

Author(s):

Mohamed Madkour ◽

Rasha Hassan ◽

Najla Sherif ◽

Samir Awadallah ◽

Ahmed Serafi ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Diseases ◽

Intermittent Fasting ◽

Gene Expressions ◽

Antioxidant Genes ◽

Funding Sources ◽

Before And After ◽

Obese Subjects ◽

Anti Inflammatory ◽

Sirt1 Gene

Abstract Objectives A mounting evidence confirms the effect of caloric restriction and intermittent fasting in ameliorating body oxidative stress and inflammation. A growing body of evidence supports that chronic inflammation and increased level of oxidative stress augment the way for the development of metabolic diseases, such as diabetes and cancers. Objectives: This research was conducted to examine the effect of Ramadan diurnal intermittent fasting (RDIF) on the gene expression of cellular metabolism (SIRT1 and SIRT3) and antioxidant genes (TFAM, SOD2, and Nrf2). Methods One-hundred fourteen (75 males and 39 females) overweight and obese subjects and twelve healthy body weight controls were followed-up before and after Ramadan. Dietary, anthropometric and biochemical assessments were performed before and at the end of Ramadan fasting month. Results Results showed that the relative gene expressions in obese subjects in comparison to counterpart expressions of controls showed a significant (P < 0.001) increase in the anti-inflammatory cytokine (IL-10), along with significant (P < 0.001) reductions in the proinflammatory cytokines (IL-6 and TNF-alpha). Expression of TFAM, SOD2, and Nrf2 significantly increased at the end of Ramadan (90.5%, 54.1%, and 411.5%, respectively). However, the metabolism-controlling gene (SIRT3) showed a highly significant (P < 0.001) downregulation accompanied by a trend for reduction in the SIRT1 gene at the end of Ramadan month, with % decrements of 61.8% and 10.4%, respectively. Conclusions Results suggest that RIF ameliorates the genetic expression of antioxidant and anti-inflammatory and metabolic regulatory genes. Thus, RIF presumably may entail a protective impact against oxidative stress and its adverse metabolic-related derangements in non-diabetic obese patients. Funding Sources University of Sharjah, UAE.

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THE CIRCADIAN RHYTHM OF INTACT PARATHYROID HORMONE (1-84) AND NEPHROGENOUS CYCLIC ADENOSINE MONOPHOSPHATE IN NORMAL MEN

Journal of Endocrinology ◽

10.1677/joe.0.121r001 ◽

1989 ◽

Vol 121 (1) ◽

pp. R1-R3 ◽

Cited By ~ 29

Author(s):

F.C. Logue ◽

W.D. Fraser ◽

D.St.J. O'Reilly ◽

G.H. Beastall

Keyword(s):

Circadian Rhythm ◽

Parathyroid Hormone ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Significant Rise ◽

Optimal Time ◽

Normal Male ◽

Intact Parathyroid Hormone ◽

Normal Men ◽

Nocturnal Rise

ABSTRACT A pronounced circadian rhythm has been demonstrated for intact parathyroid hormone (1-84) in the serum of normal male adults. The broad nocturnal rise of parathyroid hormone (1-84) secretion appears to be of physiological significance, for it is accompanied by a significant rise in nephrogenous cyclic adenosine monophosphate. The rate of return of parathyroid hormone (1-84) to baseline concentrations varies between individuals, an observation which has implications for the optimal time of sampling for the investigation of possible mild hyperparathyroidism.

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Transformations of Temporal Dimensions of Social Reality and Their Consequences for Human Resources Management

Kwartalnik Ekonomistów i Menedżerów ◽

10.5604/01.3001.0013.2336 ◽

2019 ◽

Vol 51 (1) ◽

pp. 11-21

Author(s):

Piotr Górski ◽

Ewa Ryłko

Keyword(s):

Temporal Dynamics ◽

Human Resources Management ◽

Social Process ◽

Modern Society ◽

Family Roles ◽

Resources Management ◽

Social Time ◽

The Social ◽

Temporal Dimensions ◽

The Impact

The paper considers in a historical perspective the consequences of the social time constructing for work of an organization and for individuals. It shows how this social process of time constructing is related to shaping modern society and to the changes described as post-modernity. In the context of the organization, the impact of the temporal dynamics of managers and employees on the change in the organization and in their personal life is considered. We describe the consequences of different perceptions of time for attitudes, behaviors and aspirations of contemporary employees are discussed in the context of reconciling professional and family roles.

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Influence of Long-Term Fasting on Blood Redox Status in Humans

Antioxidants ◽

10.3390/antiox9060496 ◽

2020 ◽

Vol 9 (6) ◽

pp. 496 ◽

Cited By ~ 2

Author(s):

Françoise Wilhelmi de Toledo ◽

Franziska Grundler ◽

Nikolaos Goutzourelas ◽

Fotios Tekos ◽

Eleni Vassi ◽

...

Keyword(s):

Lipid Peroxidation ◽

Body Weight ◽

Metabolic Diseases ◽

Well Being ◽

Redox Status ◽

Intermittent Fasting ◽

Fasting Period ◽

Glucose Levels ◽

Before And After

Fasting is increasingly practiced to improve health and general well-being, as well as for its cytoprotective effects. Changes in blood redox status, linked to the development of a variety of metabolic diseases, have been recently documented during calorie restriction and intermittent fasting, but not with long-term fasting (LF). We investigated some parameters of the blood redox profile in 109 subjects before and after a 10-day fasting period. Fasting resulted in a significant reduction in body weight, improved well-being and had a beneficial modulating effect on blood lipids and glucose regulation. We observed that fasting decreased lipid peroxidation (TBARS) and increased total antioxidant capacity (TAC) in plasma, concomitant with a uric acid elevation, known to be associated with fasting and did not cause gout attacks. Reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase in erythrocytes did not show significant changes. In addition, reduction in body weight, waist circumference, and glucose levels were associated to a reduced lipid peroxidation. Similar results were obtained by grouping subjects on the basis of the changes in their GSH levels, showing that a period of 10 days fasting improves blood redox status regardless of GSH status in the blood.

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