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

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
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.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals The Relationship between Frequently Used Glucose-Lowering Agents and Gut Microbiota in Type 2 Diabetes Mellitus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
You Lv ◽  
Xue Zhao ◽  
Weiying Guo ◽  
Ying Gao ◽  
Shuo Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Short Chain Fatty Acids ◽  
Current Evidence ◽  
Diabetic Patients ◽  
Glucose Lowering ◽  
Patients With Diabetes ◽  
Gastrointestinal Side Effects ◽  
Underlying Mechanisms

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: A sense of time of the glucocorticoid circadian clock: from the ontogeny to the diagnosis of Cushing’s syndrome

2018 ◽  
Vol 179 (1) ◽  
pp. R1-R18 ◽  
Author(s):  
Ayrton Custodio Moreira ◽  
Sonir Rauber Antonini ◽  
Margaret de Castro
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Clock Genes ◽  
Circadian Variation ◽  
Circadian System ◽  
Feedback Loops ◽  
Adrenal Axis ◽  
Sense Of Time ◽  
Pituitary Adrenal Axis ◽  
Hierarchical Manner

The circadian rhythm of glucocorticoids has long been recognised within the last 75 years. Since the beginning, researchers have sought to identify basic mechanisms underlying the origin and emergence of the corticosteroid circadian rhythmicity among mammals. Accordingly, Young, Hall and Rosbash, laureates of the 2017 Nobel Prize in Physiology or Medicine, as well as Takahashi’s group among others, have characterised the molecular cogwheels of the circadian system, describing interlocking transcription/translation feedback loops essential for normal circadian rhythms. Plasma glucocorticoid circadian variation depends on the expression of intrinsic clock genes within the anatomic components of the hypothalamic–pituitary–adrenal axis, which are organised in a hierarchical manner. This review presents a general overview of the glucocorticoid circadian clock mechanisms, highlighting the ontogeny of the pituitary–adrenal axis diurnal rhythmicity as well as the involvement of circadian rhythm abnormalities in the physiopathology and diagnosis of Cushing’s disease.

The effects of gut microbiota on metabolic outcomes in pregnant women and their offspring

2018 ◽  
Vol 9 (9) ◽  
pp. 4537-4547 ◽  
Author(s):  
You Lv ◽  
Zi Yan ◽  
Xue Zhao ◽  
Xiaokun Gang ◽  
Guangyu He ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gut Microbiota ◽  
Gestational Diabetes Mellitus ◽  
Pregnant Women ◽  
Metabolic Diseases ◽  
Health Issues ◽  
Metabolic Outcomes

Metabolic diseases such as gestational diabetes mellitus and obesity during pregnancy have become severe health issues due to adverse pregnant outcomes in recent years.

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

Hypertension ◽  
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.

scholarly journals Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Jie Yin ◽  
Yuying Li ◽  
Hui Han ◽  
Jie Ma ◽  
Gang Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Circadian Clock ◽  
High Fat Diet ◽  
Serum Lipid ◽  
Clock Genes ◽  
Diurnal Rhythms ◽  
High Fat ◽  
Exogenous Melatonin ◽  
Circadian Clock Genes

ABSTRACT Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice. IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.

CORTISOL CIRCADIAN RHYTHM AND INSULIN RESISTANCE IN MUSCLE: EFFECT OF DOSING AND TIMING OF HYDROCORTISONE EXPOSURE ON INSULIN SENSITIVITY IN SYNCHRONIZED MUSCLE CELLS.

2020 ◽  
Author(s):  
Mariarosaria Negri ◽  
Claudia Pivonello ◽  
Chiara Simeoli ◽  
Gilda Di Gennaro ◽  
Mary Anna Venneri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Circadian Rhythm ◽  
Insulin Sensitivity ◽  
Circadian Clock ◽  
Insulin Signaling ◽  
Clock Genes ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
Circadian Expression

Introduction/Aim: Circadian rhythm disruption is emerging as a risk factor for metabolic disorders and particularly, alterations in clock genes circadian expression have been shown to influence insulin sensitivity. Recently, the reciprocal interplay between the circadian clock machinery and HPA axis has been largely demonstrated: the circadian clock may control the physiological circadian endogenous glucocorticoids secretion and action; glucocorticoids, in turn, are potent regulator of the circadian clock and their inappropriate replacement has been associated with metabolic impairment. The aim of the current study was to investigate in vitro the interaction between the timing-of-the-day exposure to different hydrocortisone (HC) concentrations on muscle insulin sensitivity. Methods: Serum-shock synchronized mouse skeletal muscle C2C12 cells were exposed to different HC concentrations recapitulating the circulating daily physiological cortisol profile (standard cortisol profile), the circulating daily cortisol profile that reached in adrenal insufficient (AI) patients treated with once-daily MR-HC (flat cortisol profile) and treated with thrice-daily of conventional IR-HC (steep cortisol profile). The 24 hrs spontaneous oscillation of the clock genes in synchronized C2C12 cells was used to align the timing for in vitro HC exposure (Bmal1 acrophase, midphase and bathyphase) with the reference times of cortisol peaks in AI treated with IR-HC (8 am, 1 pm, 6 pm). A panel of 84 insulin sensitivity related genes and intracellular insulin signaling proteins were analyzed by RT-qPCR and western blot, respectively. Results: Only the steep profile, characterized by a higher HC exposure during Bmal1 bathyphase, produced significant downregulation in 21 insulin sensitivity-related genes. Among these, Insr, Irs1, Irs2, Pi3kca and Adipor2 were downregulated when compared the flat to the standard or steep profile. Reduced intracellular IRS1 Tyr608, AKT Ser473, AMPK Thr172 and ACC Ser79 phosphorylations were also observed. Conclusions: The current study demonstrated that is late-in-the-day cortisol exposure that modulates insulin sensitivity-related genes expression and intracellular insulin signaling in skeletal muscle cells.

Circadian clock genes and myocardial infarction in patients with type 2 diabetes mellitus

Gene ◽  
2019 ◽  
Vol 701 ◽  
pp. 98-103 ◽  
Author(s):  
Ivana Škrlec ◽  
Jakov Milić ◽  
Ines Cilenšek ◽  
Daniel Petrovič ◽  
Jasenka Wagner ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Circadian Clock ◽  
Clock Genes ◽  
Circadian Clock Genes

Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances

2008 ◽  
Vol 75 (8) ◽  
pp. 1616-1622 ◽  
Author(s):  
Hideyuki Terazono ◽  
Ahmed Hamdan ◽  
Naoya Matsunaga ◽  
Naoto Hayasaka ◽  
Hiroaki Kaji ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Clock Genes ◽  
Rhythmic Expression ◽  
Circadian Clock Genes

Enhanced effect of daytime restricted feeding on the circadian rhythm of streptozotocin-induced type 2 diabetic rats

2012 ◽  
Vol 302 (9) ◽  
pp. E1027-E1035 ◽  
Author(s):  
Tao Wu ◽  
Fen ZhuGe ◽  
Lu Sun ◽  
Yinhua Ni ◽  
Ou Fu ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Pineal Gland ◽  
Circadian Clock ◽  
Clock Genes ◽  
Activity Rhythm ◽  
Diabetic Rats ◽  
Restricted Feeding ◽  
Behavioral Rhythm ◽  
Type 2 Diabetic

There is increasing awareness of the link between impaired circadian clocks and multiple metabolic diseases. However, the impairment of the circadian clock by type 2 diabetes has not been fully elucidated. To understand whether and how the function of circadian clock is impaired under the diabetic condition, we examined not only the expression of circadian genes in the heart and pineal gland but also the behavioral rhythm of type 2 diabetic and control rats in both the nighttime restricted feeding (NRF) and daytime restricted feeding (DRF) conditions. In the NRF condition, the circadian expression of clock genes in the heart and pineal gland was conserved in the diabetic rats, being similar to that in the control rats. DRF shifted the circadian phases of peripheral clock genes more efficiently in the diabetic rats than those in the control rats. Moreover, the activity rhythm of rats in the diabetic group was completely shifted from the dark phase to the light phase after 5 days of DRF treatment, whereas the activity rhythm of rats in the control group was still under the control of the suprachiasmatic nucleus (SCN) after the same DRF treatment. Furthermore, the serum glucose rhythm of type 2 diabetic rats was also shifted and controlled by the external feeding schedule, ignoring the SCN rhythm. Therefore, DRF shows stronger effect on the reentrainment of circadian rhythm in the type 2 diabetic rats, suggesting that the circadian system in diabetes is unstable and more easily shifted by feeding stimuli.

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