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González-Suárez M, Aguilar-Arnal L. Histone methylation: at the crossroad between circadian rhythms in transcription and metabolism. Front Genet 2024; 15:1343030. [PMID: 38818037 PMCID: PMC11137191 DOI: 10.3389/fgene.2024.1343030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 04/24/2024] [Indexed: 06/01/2024] Open
Abstract
Circadian rhythms, essential 24-hour cycles guiding biological functions, synchronize organisms with daily environmental changes. These rhythms, which are evolutionarily conserved, govern key processes like feeding, sleep, metabolism, body temperature, and endocrine secretion. The central clock, located in the suprachiasmatic nucleus (SCN), orchestrates a hierarchical network, synchronizing subsidiary peripheral clocks. At the cellular level, circadian expression involves transcription factors and epigenetic remodelers, with environmental signals contributing flexibility. Circadian disruption links to diverse diseases, emphasizing the urgency to comprehend the underlying mechanisms. This review explores the communication between the environment and chromatin, focusing on histone post-translational modifications. Special attention is given to the significance of histone methylation in circadian rhythms and metabolic control, highlighting its potential role as a crucial link between metabolism and circadian rhythms. Understanding these molecular intricacies holds promise for preventing and treating complex diseases associated with circadian disruption.
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Affiliation(s)
| | - Lorena Aguilar-Arnal
- Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
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2
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Rabadán-Chávez G, Díaz de la Garza RI, Jacobo-Velázquez DA. White adipose tissue: Distribution, molecular insights of impaired expandability, and its implication in fatty liver disease. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166853. [PMID: 37611674 DOI: 10.1016/j.bbadis.2023.166853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 07/17/2023] [Accepted: 08/18/2023] [Indexed: 08/25/2023]
Abstract
We are far behind the 2025 World Health Organization (WHO) goal of a zero increase in obesity. Close to 360 million people in Latin America and the Caribbean are overweight, with the highest rates observed in the Bahamas, Mexico, and Chile. To achieve relevant progress against the obesity epidemic, scientific research is essential to establish uniform practices in the study of obesity pathophysiology (using pre-clinical and clinical models) that ensure accuracy, reproducibility, and transcendent outcomes. The present review focuses on relevant aspects of white adipose tissue (WAT) expansion, underlying mechanisms of inefficient expandability, and its repercussion in ectopic lipid accumulation in the liver during nutritional abundance. In addition, we highlight the potential role of disrupted circadian rhythm in WAT metabolism. Since genetic factors also play a key role in determining an individual's predisposition to weight gain, we describe the most relevant genes associated with obesity in the Mexican population, underlining that most of them are related to appetite control.
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Affiliation(s)
- Griselda Rabadán-Chávez
- Tecnologico de Monterrey, Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, NL, Mexico
| | - Rocío I Díaz de la Garza
- Tecnologico de Monterrey, Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, NL, Mexico; Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Campus Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, NL, Mexico.
| | - Daniel A Jacobo-Velázquez
- Tecnologico de Monterrey, Institute for Obesity Research, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, NL, Mexico; Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Campus Guadalajara, Av. General Ramon Corona 2514, C.P. 45201 Zapopan, Jalisco, Mexico.
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3
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He SK, Wang JH, Li T, Yin S, Cui JW, Xiao YF, Tang Y, Wang J, Bai YJ. Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review. Front Endocrinol (Lausanne) 2023; 14:1293685. [PMID: 38089624 PMCID: PMC10711275 DOI: 10.3389/fendo.2023.1293685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 11/08/2023] [Indexed: 12/18/2023] Open
Abstract
The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.
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Affiliation(s)
- Si-Ke He
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Jia-Hao Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Li
- Department of Urology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Shan Yin
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Jian-Wei Cui
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yun-Fei Xiao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yin Tang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Jia Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yun-Jin Bai
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
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Moon HY, Jeong IC. The effect of voluntary exercise on light cycle stress-induced metabolic resistance. Phys Act Nutr 2023; 27:1-9. [PMID: 37946440 PMCID: PMC10636503 DOI: 10.20463/pan.2023.0022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/09/2023] [Accepted: 08/16/2023] [Indexed: 11/12/2023] Open
Abstract
PURPOSE Disruption of circadian genes affects metabolic homeostasis. Regular exercise programs prevent metabolic dysfunction and alter circadian gene expression In this study, we investigated whether exercise affects light stress-induced circadian rhythm derangement and metabolic resistance. METHODS A circadian rhythm derangement mouse model was designed by extending the light exposure by two hours (14 L/10 D) for three weeks. Nine-weekold male mice were single-caged and divided into four groups: sedentary groups with or without light stress, and voluntary wheel-trained groups with or without light stress. In addition, differentiated myotubes were cultured in the presence of dexamethasone with or without 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR). The comprehensive laboratory animal monitoring system was used to analyze the metabolic changes in mice. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the mRNA expression levels of circadian genes in animal and cell culture models. RESULTS Three weeks of light stress reduced the running distance and increased the weight of mice. In addition, VO2 consumption and heat production were increased during the night cycle under non-stress conditions but not under stress conditions. PCR analysis revealed that exercise and stress altered the expression levels of circadian genes in the hypothalamus and quadriceps muscles. mRNA expression levels of period circadian regulator 1 were downregulated in the quadriceps muscles of the stressed sedentary group compared to that in muscles of the non-stressed sedentary group. Furthermore, differentiated myotube cells cultured in the presence of dexamethasone, with or without AICAR, showed distinct oscillation patterns at various time points. CONCLUSION Our study demonstrates that exercise partially prevents metabolic disruption by regulating the circadian gene expression in skeletal muscles.
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Affiliation(s)
- Hyo Youl Moon
- Department of Physical Education, Seoul National University, Seoul, Republic of Korea
- Institute on Aging, Seoul National University, Seoul, Republic of Korea
| | - In Cheol Jeong
- School of Artificial Intelligence Convergence, Hallym University, Chuncheon, Republic of Korea
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Tsameret S, Chapnik N, Froy O. Effect of early vs. late time-restricted high-fat feeding on circadian metabolism and weight loss in obese mice. Cell Mol Life Sci 2023; 80:180. [PMID: 37329359 PMCID: PMC11072437 DOI: 10.1007/s00018-023-04834-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 06/05/2023] [Accepted: 06/06/2023] [Indexed: 06/19/2023]
Abstract
Time-restricted feeding (TRF) limits the time and duration of food availability without calorie reduction. Although a high-fat (HF) diet leads to disrupted circadian rhythms, TRF can prevent metabolic diseases, emphasizing the importance of the timing component. However, the question of when to implement the feeding window and its metabolic effect remains unclear, specifically in obese and metabolically impaired animals. Our aim was to study the effect of early vs. late TRF-HF on diet-induced obese mice in an 8:16 light-dark cycle. C57BL male mice were fed ad libitum a high-fat diet for 14 weeks after which they were given the same food during the early (E-TRF-HF) or late (L-TRF-HF) 8 h of the dark phase for 5 weeks. The control groups were fed ad libitum either a high-fat (AL-HF) or a low-fat diet (AL-LF). Respiratory exchange ratio (RER) was highest for the AL-LF group and the lowest for the AL-HF group. E-TRF-HF led to lower body weight and fat depots, lower glucose, C-peptide, insulin, cholesterol, leptin, TNFα, and ALT levels compared with L-TRF-HF- and AL-HF-fed mice. TRF-HF regardless whether it was early or late led to reduced inflammation and fat accumulation compared with AL-HF-fed mice. E-TRF-HF led to advanced liver circadian rhythms with higher amplitudes and daily expression levels of clock proteins. In addition, TRF-HF led to improved metabolic state in muscle and adipose tissue. In summary, E-TRF-HF leads to increased insulin sensitivity and fat oxidation and decreased body weight, fat profile and inflammation contrary to AL-HF-fed, but comparable to AL-LF-fed mice. These results emphasize the importance of timed feeding compared to ad libitum feeding, specifically to the early hours of the activity period.
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Affiliation(s)
- Shani Tsameret
- Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 76100, Rehovot, Israel
| | - Nava Chapnik
- Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 76100, Rehovot, Israel
| | - Oren Froy
- Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 76100, Rehovot, Israel.
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6
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Abstract
The circadian clock plays an essential role in coordinating feeding and metabolic rhythms with the light/dark cycle. Disruption of clocks is associated with increased adiposity and metabolic disorders, whereas aligning feeding time with cell-autonomous rhythms in metabolism improves health. Here, we provide a comprehensive overview of recent literature in adipose tissue biology as well as our understanding of molecular mechanisms underlying the circadian regulation of transcription, metabolism, and inflammation in adipose tissue. We highlight recent efforts to uncover the mechanistic links between clocks and adipocyte metabolism, as well as its application to dietary and behavioral interventions to improve health and mitigate obesity.
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Affiliation(s)
- Chelsea Hepler
- Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
| | - Joseph Bass
- Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
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7
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Verma AK, Singh S, Rizvi SI. Aging, circadian disruption and neurodegeneration: Interesting interplay. Exp Gerontol 2023; 172:112076. [PMID: 36574855 DOI: 10.1016/j.exger.2022.112076] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 11/26/2022] [Accepted: 12/22/2022] [Indexed: 12/26/2022]
Abstract
The circadian system is an intricate molecular network of coordinating circadian clocks that organize the internal synchrony of the organism in response to the environment. These rhythms are maintained by genetically programmed positive and negative auto-regulated transcriptional and translational feedback loops that sustain 24-hour oscillations in mRNA and protein components of the endogenous circadian clock. Since inter and intracellular activity of the central pacemaker appears to reduce with aging, the interaction between the circadian clock and aging continues to elude our understanding. In this review article, we discuss circadian clock components at the molecular level and how aging adversely affects circadian clock functioning in rodents and humans. The natural decline in melatonin levels with aging strongly contributes to circadian dysregulation resulting in the development of neurological anomalies. Additionally, inappropriate environmental conditions such as Artificial Light at Night (ALAN) can cause circadian disruption or chronodisruption (CD) which can result in a variety of pathological diseases, including premature aging. Furthermore, we summarize recent evidence suggesting that CD may also be a predisposing factor for the development of age-related neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), although more investigation is required to prove this link. Finally, certain chrono-enhancement approaches have been offered as intervention strategies to prevent, alleviate, or mitigate the impacts of CD. This review thus aims to bring together recent advancements in the chronobiology of the aging process, as well as its role in NDDs.
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Affiliation(s)
- Avnish Kumar Verma
- Department of Biochemistry, University of Allahabad, Allahabad 211002, India
| | - Sandeep Singh
- Department of Biochemistry, University of Allahabad, Allahabad 211002, India; Psychedelics Research Group, Biological Psychiatry Laboratory and Hadassah BrainLabs, Hadassah Medical Center, Hebrew University, Jerusalem, Israel
| | - Syed Ibrahim Rizvi
- Department of Biochemistry, University of Allahabad, Allahabad 211002, India.
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Martín-Reyes F, Ho-Plagaro A, Rodríguez-Díaz C, Lopez-Gómez C, Garcia-Serrano S, de Los Reyes DR, Gonzalo M, Fernández-Garcia JC, Montiel-Casado C, Fernández-Aguilar JL, Fernández JR, García-Fuentes E, Rodríguez-Pacheco F. Oleic acid regulates the circadian rhythm of adipose tissue in obesity. Pharmacol Res 2023; 187:106579. [PMID: 36435269 DOI: 10.1016/j.phrs.2022.106579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 11/21/2022] [Accepted: 11/22/2022] [Indexed: 11/24/2022]
Abstract
The effect of oleic acid (OA) on the regulation of the circadian rhythm present in human visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with morbid obesity has not been analyzed yet. VAT and SAT explants from patients with morbid obesity were incubated with OA to analyze the circadian regulation of clock and other genes related to lipid metabolism (SREBP-1c, FAS, LPL and CPT1), and their association with baseline variables and the improvement of these patients after bariatric surgery. There were significant differences in amplitude and acrophase in VAT with respect to SAT. In VAT, body weight negatively correlated with BMAL1 and CRY1 amplitude, and REVERBα acrophase; body mass index (BMI) negatively correlated with REVERBα acrophase; and waist circumference negatively correlated with PER3 acrophase. In SAT, BMI negatively correlated with CLOCK amplitude, and CLOCK, REVERBα and CRY2 MESOR; and waist circumference negatively correlated with PER3 amplitude and acrophase. A greater short-term improvement of body weight, BMI and waist circumference in patients with morbid obesity after bariatric surgery was associated with a lower CRY1 and CRY2 amplitude and an earlier PER1 and PER3 acrophase in SAT. OA produced a more relevant circadian rhythm and increased the amplitude of most clock genes and lipid metabolism-related genes. OA regulated the acrophase of most clock genes in VAT and SAT, placing CLOCK/BMAL1 in antiphase with regard to the other genes. OA increased the circadian rhythmicity, although with slight differences between adipose tissues. These differences could determine its different behavior in obesity.
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Affiliation(s)
- Flores Martín-Reyes
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Ailec Ho-Plagaro
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Cristina Rodríguez-Díaz
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Carlos Lopez-Gómez
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Sara Garcia-Serrano
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario, Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas-CIBERDEM, Málaga, Spain
| | - Dámaris Rodriguez de Los Reyes
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Montserrat Gonzalo
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario, Málaga, Spain
| | - Jose C Fernández-Garcia
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario, Málaga, Spain
| | - Custodia Montiel-Casado
- Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario, Málaga, Spain
| | - Jose L Fernández-Aguilar
- Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario, Málaga, Spain
| | - José R Fernández
- Bioengeneering & Chronobiology Labs, atlanTTic Research Center, University of Vigo, Spain
| | - Eduardo García-Fuentes
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain; CIBER de Enfermedades Hepáticas y Digestivas-CIBEREHD, Málaga, Spain.
| | - Francisca Rodríguez-Pacheco
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas-CIBERDEM, Málaga, Spain
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Circadian mechanism disruption is associated with dysregulation of inflammatory and immune responses: a systematic review. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2022. [DOI: 10.1186/s43088-022-00290-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
AbstractThe 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.
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10
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Chan K, Wong FS, Pearson JA. Circadian rhythms and pancreas physiology: A review. Front Endocrinol (Lausanne) 2022; 13:920261. [PMID: 36034454 PMCID: PMC9399605 DOI: 10.3389/fendo.2022.920261] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 07/21/2022] [Indexed: 11/29/2022] Open
Abstract
Type 2 diabetes mellitus, obesity and metabolic syndrome are becoming more prevalent worldwide and will present an increasingly challenging burden on healthcare systems. These interlinked metabolic abnormalities predispose affected individuals to a plethora of complications and comorbidities. Furthermore, diabetes is estimated by the World Health Organization to have caused 1.5 million deaths in 2019, with this figure projected to rise in coming years. This highlights the need for further research into the management of metabolic diseases and their complications. Studies on circadian rhythms, referring to physiological and behavioral changes which repeat approximately every 24 hours, may provide important insight into managing metabolic disease. Epidemiological studies show that populations who are at risk of circadian disruption such as night shift workers and regular long-haul flyers are also at an elevated risk of metabolic abnormalities such as insulin resistance and obesity. Aberrant expression of circadian genes appears to contribute to the dysregulation of metabolic functions such as insulin secretion, glucose homeostasis and energy expenditure. The potential clinical implications of these findings have been highlighted in animal studies and pilot studies in humans giving rise to the development of circadian interventions strategies including chronotherapy (time-specific therapy), time-restricted feeding, and circadian molecule stabilizers/analogues. Research into these areas will provide insights into the future of circadian medicine in metabolic diseases. In this review, we discuss the physiology of metabolism and the role of circadian timing in regulating these metabolic functions. Also, we review the clinical aspects of circadian physiology and the impact that ongoing and future research may have on the management of metabolic disease.
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Affiliation(s)
- Karl Chan
- Diabetes Research Group, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
| | - F. Susan Wong
- Diabetes Research Group, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
- Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, United Kingdom
| | - James Alexander Pearson
- Diabetes Research Group, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
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11
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Mammalian PERIOD2 regulates H2A.Z incorporation in chromatin to orchestrate circadian negative feedback. Nat Struct Mol Biol 2022; 29:549-562. [PMID: 35606517 DOI: 10.1038/s41594-022-00777-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 04/11/2022] [Indexed: 11/08/2022]
Abstract
Mammalian circadian oscillators are built on a feedback loop in which the activity of the transcription factor CLOCK-BMAL1 is repressed by the PER-CRY complex. Here, we show that murine Per-/- fibroblasts display aberrant nucleosome occupancy around transcription start sites (TSSs) and at promoter-proximal and distal CTCF sites due to impaired histone H2A.Z deposition. Knocking out H2A.Z mimicked the Per null chromatin state and disrupted cellular rhythms. We found that endogenous mPER2 complexes retained CTCF as well as the specific H2A.Z-deposition chaperone YL1-a component of the ATP-dependent remodeler SRCAP and p400-TIP60 complex. While depleting YL1 or mutating chaperone-binding sites on H2A.Z lengthened the circadian period, H2A.Z deletion abrogated BMAL1 chromatin recruitment and promoted its proteasomal degradation. We propose that a PER2-mediated H2A.Z deposition pathway (1) compacts CLOCK-BMAL1 binding sites to establish negative feedback, (2) organizes circadian chromatin landscapes using CTCF and (3) bookmarks genomic loci for BMAL1 binding to impinge on the positive arm of the subsequent cycle.
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12
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Grasset E, Puel A, Charpentier J, Klopp P, Christensen JE, Lelouvier B, Servant F, Blasco-Baque V, Tercé F, Burcelin R. Gut microbiota dysbiosis of type 2 diabetic mice impairs the intestinal daily rhythms of GLP-1 sensitivity. Acta Diabetol 2022; 59:243-258. [PMID: 34648088 DOI: 10.1007/s00592-021-01790-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023]
Abstract
The gut-brain-beta cell glucagon-like peptide-1 (GLP-1)-dependent axis and the clock genes both control insulin secretion. Evidence shows that a keystone of this molecular interaction could be the gut microbiota. We analyzed in mice the circadian profile of GLP-1 sensitivity on insulin secretion and the impact of the autonomic neuropathy, antibiotic treated in different diabetic mouse models and in germ-free colonized mice. We show that GLP-1sensitivity is maximal during the dark feeding period, i.e., the postprandial state. Coincidently, the ileum expression of GLP-1 receptor and peripherin is increased and tightly correlated with a subset of clock gene. Since both are markers of enteric neurons, it suggests a role in the gut-brain-beta cell GLP-1-dependent axis. We evaluated the importance of gut microbiota dysbiosis and found that the abundance of ileum bacteria, particularly Ruminococcaceae and Lachnospiraceae, oscillated diurnally, with a maximum during the dark period, along with expression patterns of a subset of clock genes. This diurnal pattern of circadian gene expression and Lachnospiraceae abundance was also observed in two separate mouse models of gut microbiota dysbiosis and of autonomic neuropathy with impaired GLP-1 sensitivity (1.high-fat diet-fed type 2 diabetic, 2.antibiotic-treated/germ-free mice). Our data show that GLP-1 sensitivity relies on specific pattern of intestinal clock gene expression and specific gut bacteria. This new statement opens opportunities to treat diabetic patient with GLP-1-based therapies by using on a possible pre/probiotic co-treatment to improve the time-dependent efficiency of these therapies.
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Affiliation(s)
- Estelle Grasset
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France.
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France.
| | - Anthony Puel
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Julie Charpentier
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Pascale Klopp
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Jeffrey E Christensen
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Benjamin Lelouvier
- Vaiomer SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670, Labège Innopole, France
| | - Florence Servant
- Vaiomer SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670, Labège Innopole, France
| | - Vincent Blasco-Baque
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - François Tercé
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Rémy Burcelin
- Directeur de Recherche Inserm I²MC, Institut des Maladies Métaboliques et Cardiovasculaires, Inserm U 1027, Rue Jean Poulhès, 31400, Toulouse, France.
- Research Director Inserm I²MC, Institute for research on cardiometabolic diseases, Inserm U 1027, Rue Jean Poulhès, 31400, Toulouse, France.
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13
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Li T, Bai Y, Jiang Y, Jiang K, Tian Y, Wang Z, Ban Y, Liang X, Luo G, Sun F. Potential Effect of the Circadian Clock on Erectile Dysfunction. Aging Dis 2022; 13:8-23. [PMID: 35111358 PMCID: PMC8782551 DOI: 10.14336/ad.2021.0728] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 07/28/2021] [Indexed: 12/03/2022] Open
Abstract
The circadian rhythm is an internal timing system, which is generated by circadian clock genes. Because the circadian rhythm regulates numerous cellular, behavioral, and physiological processes, organisms have evolved with intrinsic biological rhythms to adapt the daily environmental changes. A variety of pathological events occur at specific times, while disturbed rhythms can lead to metabolic syndrome, vascular dysfunction, inflammatory disorders, and cancer. Therefore, the circadian clock is considered closely related to various diseases. Recently, accumulated data have shown that the penis is regulated by the circadian clock, while erectile function is impaired by an altered sleep-wake cycle. The circadian rhythm appears to be a novel therapeutic target for preventing and managing erectile dysfunction (ED), although research is still progressing. In this review, we briefly summarize the superficial interactions between the circadian clock and erectile function, while focusing on how disturbed rhythms contribute to risk factors of ED. These risk factors include NO/cGMP pathway, atherosclerosis, diabetes mellitus, lipid abnormalities, testosterone deficiency, as well as dysfunction of endothelial and smooth muscle cells. On the basis of recent findings, we discuss the potential role of the circadian clock for future therapeutic strategies on ED, although further relevant research needs to be performed.
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Affiliation(s)
- Tao Li
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
| | - Yunjin Bai
- Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Yiting Jiang
- Department of Otorhinolaryngology, The Ninth People’s Hospital of Chongqing, Chongqing, China
| | - Kehua Jiang
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
| | - Ye Tian
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
| | - Zhen Wang
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
| | - Yong Ban
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
| | - Xiangyi Liang
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
| | - Guangheng Luo
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
- Correspondence should be addressed to: Dr. Fa Sun, Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China. .
| | - Fa Sun
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.
- Correspondence should be addressed to: Dr. Fa Sun, Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China. .
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14
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Peng L, Zhang K, Chen K. Period circadian clock 3 inhibits palmitic acid-induced oxidative stress and inflammatory factor secretion in podocytes. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2021; 46:1177-1186. [PMID: 34911851 PMCID: PMC10929857 DOI: 10.11817/j.issn.1672-7347.2021.210019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVES High fat-induced podocyte injury is one of the important factors leading to obesity related nephropathy (ORG), but the mechanism is not clear. This study aims to explore the mechanism of period circadian clock 3 (PER3) in the oxidative stress and inflammation induced by palmitic acid (PA) in podocytes. METHODS The C57BL/6J mice were fed with chow and high-fat diet for 16 weeks. The PER3 expression in kidney tissues were detected in the normal body weight group and the obesity group. The PER3 mRNA and protein expression were detected after the podocytes were induced with different concentrations (0, 50, 150 and 300 μmol/L) of PA for 48 h. The PER3 mRNA and protein expression were detected after the podocytes were induced with 150 μmol/L PA for 0, 24, 36, and 48 h. Triglyceride (TG) levels were examined in the PA group, the adenovirus (ad)-PER3+PA group, and the siRNA-PER+PA group after the podocytes were transfected by Ad-PER3 or small interfering RNA (siRNA)-PER3 for 48 h and subsequently were induced with 150 μmol/L PA for 48 h. The differential gene expression was detected using RNA sequencing (RNA-seq) after podocytes were transfected by siRNA-PER3 (siRNA-PER3 group) and siRNA-control (siRNA-control group), respectively. The mRNA levels of nephrin, podocin, podocalyxin, podoplanin, superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), catalase (CAT), and the levels of malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-2 (IL-2) were detected after podocytes were transfected with Ad-PER3 or Ad-control for 48 h and then they were induced by 150 μmol/L PA for 48 h. RESULTS The PER3 was down-regulated in the obesity group compared with the normal body weight group (P<0.05), and the PER3 was significantly down-regulated after the podocytes were treated with 150 μmol/L for 48 h compared with 0, 24, and 36 h (all P<0.01). The TG contents were significantly decreased in the Ad-PER3+PA group compared with the PA group (P<0.05). On the contrary, TG contents were increased in the siRNA-PER3+PA group compared with the PA group (P<0.05). The RNA-seq results showed that: compared with the siRNA-control group, the differential genes in the siRNA-PER3 group were enriched in different pathways including oxidative phosphorylation, TNF signaling pathway, extracellular matrix receptor interaction, fatty acid metabolism, and fatty acid degradation (all P<0.05). The podocyte marker genes (nephrin, podocin, podocalyxin and podoplanin), oxidative stress (SOD1, GPX1, CAT and GSH), and inflammation factors (TNF-α, IL-6, IL-1β and IL-2) were significantly down-regulated in the Ad-PER3+PA group compared with the PA group (all P<0.05). CONCLUSIONS PER3 can decrease the PA-induced oxidative stress and inflammatory factor secretion via inhibiting the lipogenesis in podocytes.
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Affiliation(s)
- Lin Peng
- Department of Nephrology, First Hospital of Changsha, Changsha 410005.
| | - Keke Zhang
- Department of Endorcrinology, Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Ke Chen
- Department of Endorcrinology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
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15
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Guan D, Lazar MA. Interconnections between circadian clocks and metabolism. J Clin Invest 2021; 131:e148278. [PMID: 34338232 DOI: 10.1172/jci148278] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Circadian rhythms evolved through adaptation to daily light/dark changes in the environment; they are believed to be regulated by the core circadian clock interlocking feedback loop. Recent studies indicate that each core component executes general and specific functions in metabolism. Here, we review the current understanding of the role of these core circadian clock genes in the regulation of metabolism using various genetically modified animal models. Additionally, emerging evidence shows that exposure to environmental stimuli, such as artificial light, unbalanced diet, mistimed eating, and exercise, remodels the circadian physiological processes and causes metabolic disorders. This Review summarizes the reciprocal regulation between the circadian clock and metabolism, highlights remaining gaps in knowledge about the regulation of circadian rhythms and metabolism, and examines potential applications to human health and disease.
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Affiliation(s)
- Dongyin Guan
- Institute for Diabetes, Obesity, and Metabolism.,Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and
| | - Mitchell A Lazar
- Institute for Diabetes, Obesity, and Metabolism.,Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and.,Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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16
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Azevedo PGD, Miranda LR, Nicolau ES, Alves RB, Bicalho MAC, Couto PP, Ramos AV, Souza RPD, Longhi R, Friedman E, Marco LD, Bastos-Rodrigues L. Genetic association of the PERIOD3 (PER3) Clock gene with extreme obesity. Obes Res Clin Pract 2021; 15:334-338. [PMID: 34215556 DOI: 10.1016/j.orcp.2021.06.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 07/28/2020] [Accepted: 06/11/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND Obesity has reached epidemic proportions worldwide, affecting life quality and span. Susceptibility to obesity is partly mediated by genetic differences. Indeed, several genes from the clock gene family have already been shown to be intimately associated with obesity in diverse ethnic groups. In the present study, an association between BMI and the rs707467, rs228697 and rs228729 PER3 (Period Circadian Clock 3) polymorphisms in subjects with class II (BMI ≥ 35.0-39.9 kg/m2) and class III obesity (>40 kg/m2, extreme obesity) were carried out using TaqMan real-time PCR. Overall, 259 Brazilian adults were genotyped, of whom 122 had class II or III obesity (BMI ≥ 35.0 kg/m2) and 137 were controls having normal weight (BMI > 18.5 and <24.9 kg/m2). RESULTS PER3 tag SNP (rs228729) shows a significant association with extreme obesity (1000 permutation p = 0.03 and p = 0.04), for genotype and allele frequency respectively) and a haplotype among the three assessed SNPs (alleles G/T/A, rs228697, rs228729, and rs707467, respectively, 1000 permutation p = 0.03) was significantly more prevalent in the group with obesity. CONCLUSION This exploratory association study suggests that PER3 rs228729 may be associated with extreme obesity in Brazilian adults, however, replication is needed.
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Affiliation(s)
- Pedro Guimarães de Azevedo
- Centro de Tecnologia em Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Brazil
| | - Luana Reis Miranda
- Centro de Tecnologia em Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Brazil
| | - Eduardo Souza Nicolau
- Centro de Tecnologia em Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Brazil
| | - Rayane Benfica Alves
- Centro de Tecnologia em Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Brazil
| | | | - Patrícia Pereira Couto
- Centro de Tecnologia em Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Brazil
| | | | - Renan Pedra de Souza
- Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Rafael Longhi
- Department of Nutrition, Universidade Federal de Minas Gerais, Belo Horizonte, MG 35010-177, Brazil
| | - Eitan Friedman
- The Suzanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Tel Hashomer, the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Luiz De Marco
- Department of Surgery, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Luciana Bastos-Rodrigues
- Department of Nutrition, Universidade Federal de Minas Gerais, Belo Horizonte, MG 35010-177, Brazil.
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17
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Wan X, Zhu L, Zhao L, Peng L, Xiong J, Yang W, Yuan J, Liang F, Zhang K, Chen K. hPER3 promotes adipogenesis via hHSP90AA1-mediated inhibition of Notch1 pathway. Cell Death Dis 2021; 12:301. [PMID: 33741899 PMCID: PMC7979882 DOI: 10.1038/s41419-021-03584-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/26/2021] [Accepted: 03/03/2021] [Indexed: 12/17/2022]
Abstract
The period circadian regulator 3 (PER3) has been reported to play a negative role in human immortalized bone marrow-derived Scp-1 cells (iBMSCs) and patient adipose-derived stromal cells (PASCs) or a negative/positive role in mice adipogenesis. However, human PER3 (hPER3) was identified as a positive regulator of human adipose tissue-derived stromal cells (hADSCs) adipogenesis in this study. Silencing or overexpression of hPER3 in hADSCs inhibited and promoted adipogenesis in vitro. In vivo, the overexpression of hPER3 increased high-fat diet-induced inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) forms, increasing systemic glucose intolerance and insulin resistance. Molecularly, hPER3 does not interact with hPPARγ, but represses Notch1 signaling pathway to enhance adipogenesis by interacting with hHSP90AA1, which is able to combine with the promoter of hNotch1 and inactivate its expression. Thus, our study revealed hPER3 as a critical positive regulator of hADSCs adipogenesis, which was different from the other types of cells, providing a critical role of it in treating obesity.
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Affiliation(s)
- Xinxing Wan
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Liyong Zhu
- Department of Bariatric and Metabolic Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Liling Zhao
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Lin Peng
- Department of Nephrology, The First Hospital of Changsha, Changsha, Hunan, 410005, China
| | - Jing Xiong
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Wenjun Yang
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Jingjing Yuan
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Fang Liang
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Keke Zhang
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China
| | - Ke Chen
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
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18
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Does a high-fat diet affect the circadian clock, or is it the other way around? A systematic review. Nutr Res 2020; 84:1-13. [PMID: 33213889 DOI: 10.1016/j.nutres.2020.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 09/25/2020] [Accepted: 10/08/2020] [Indexed: 10/23/2022]
Abstract
This paper reviews studies that addressed the influence of diet on circadian rhythmicity in mice and, in turn, circadian clock chronodisruption and its role in the development of metabolic disorders. Studies from the past 14 years were selected via a systematic search conducted using the PubMed electronic database. After applying the inclusion and exclusion criteria, 291 studies were selected, of which 13 were chosen using the following inclusion criteria: use of a high-fat diet for mice, evaluation of clock gene expression, and the association between chronodisruption and lipid metabolism disorders. These studies reported changes in animals' biological clock when they developed metabolic disorders by consuming a high-fat diet. It was also evident that some clock gene mutations or deletions triggered metabolic changes. Disturbances of clock gene machinery may play important roles in lipid metabolism and the development of atherosclerotic processes. However, many metabolic processes also affect the function of clock genes and circadian systems. In summary, this review's results may provide new insights into the reciprocal regulation of energy homeostasis and the biological clock.
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19
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Yan R, Ho C, Zhang X. Interaction between Tea Polyphenols and Intestinal Microbiota in Host Metabolic Diseases from the Perspective of the Gut–Brain Axis. Mol Nutr Food Res 2020; 64:e2000187. [DOI: 10.1002/mnfr.202000187] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/29/2020] [Indexed: 12/17/2022]
Affiliation(s)
- Ruonan Yan
- Department of Food Science and EngineeringNingbo University Ningbo 315211 P. R. China
| | - Chi‐Tang Ho
- Department of Food ScienceRutgers University New Brunswick NJ 08901 USA
| | - Xin Zhang
- Department of Food Science and EngineeringNingbo University Ningbo 315211 P. R. China
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20
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Fatima N, Rana S. Metabolic implications of circadian disruption. Pflugers Arch 2020; 472:513-526. [PMID: 32363530 DOI: 10.1007/s00424-020-02381-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 04/16/2020] [Accepted: 04/17/2020] [Indexed: 01/20/2023]
Abstract
Circadian rhythms are generated by the circadian clock, a self-sustained internal timing system that exhibits 24-h rhythms in the body. In mammals, circadian rhythms are driven by a central clock located in suprachiasmatic nucleus and various peripheral clocks located in different tissues and organs of the body. Many cellular, behavioral, and physiological processes are regulated by the circadian clock in coordination with environmental cues. The process of metabolism is also under circadian regulation. Loss of synchronization between the internal clock and environmental zeitgebers results in disruption of the circadian rhythms that seriously impacts metabolic homeostasis leading to changed eating behavior, altered glucose and lipid metabolism, and weight gain. This in turn augments the risk of having various cardio-metabolic disorders such as obesity, diabetes, metabolic syndrome, and cardiovascular disease. This review sheds light on circadian rhythms and their role in metabolism with the identification of gaps in the current knowledge that remain to be explored in these fields. In this review, the molecular mechanisms underlying circadian rhythms have been elaborated first. Then, the focus has been kept on explaining the physiological significance of circadian rhythms in regulating metabolism. Finally, the implications for metabolism when these rhythms are disrupted due to genetic mutations or social and occupational needs enforced by modern lifestyle have been discussed.
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Affiliation(s)
- Narjis Fatima
- Molecular Biology and Human Genetics Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan
| | - Sobia Rana
- Molecular Biology and Human Genetics Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan.
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21
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Van der Veen DR, Laing EE, Bae SE, Johnston JD, Dijk DJ, Archer SN. A Topological Cluster of Differentially Regulated Genes in Mice Lacking PER3. Front Mol Neurosci 2020; 13:15. [PMID: 32116548 PMCID: PMC7031657 DOI: 10.3389/fnmol.2020.00015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 01/20/2020] [Indexed: 11/13/2022] Open
Abstract
Polymorphisms in the human circadian clock gene PERIOD3 (PER3) are associated with a wide variety of phenotypes such as diurnal preference, delayed sleep phase disorder, sleep homeostasis, cognitive performance, bipolar disorder, type 2 diabetes, cardiac regulation, cancer, light sensitivity, hormone and cytokine secretion, and addiction. However, the molecular mechanisms underlying these phenotypic associations remain unknown. Per3 knockout mice (Per3-/- ) have phenotypes related to activity, sleep homeostasis, anhedonia, metabolism, and behavioral responses to light. Using a protocol that induces behavioral differences in response to light in wild type and Per3-/- mice, we compared genome-wide expression in the eye and hypothalamus in the two genotypes. Differentially expressed transcripts were related to inflammation, taste, olfactory and melatonin receptors, lipid metabolism, cell cycle, ubiquitination, and hormones, as well as receptors and channels related to sleep regulation. Differentially expressed transcripts in both tissues co-localized with Per3 on an ∼8Mbp region of distal chromosome 4. The most down-regulated transcript is Prdm16, which is involved in adipocyte differentiation and may mediate altered body mass accumulation in Per3-/- mice. eQTL analysis with BXD mouse strains showed that the expression of some of these transcripts and also others co-localized at distal chromosome 4, is correlated with brain tissue expression levels of Per3 with a highly significant linkage to genetic variation in that region. These data identify a cluster of transcripts on mouse distal chromosome 4 that are co-regulated with Per3 and whose expression levels correlate with those of Per3. This locus lies within a topologically associating domain island that contains many genes with functional links to several of the diverse non-circadian phenotypes associated with polymorphisms in human PER3.
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Affiliation(s)
- Daan R Van der Veen
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
| | - Emma E Laing
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
| | - Sung-Eun Bae
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
| | - Jonathan D Johnston
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
| | - Derk-Jan Dijk
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.,UK Dementia Research Institute, London, United Kingdom
| | - Simon N Archer
- School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
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22
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Kolbe I, Brehm N, Oster H. Interplay of central and peripheral circadian clocks in energy metabolism regulation. J Neuroendocrinol 2019; 31:e12659. [PMID: 30415480 DOI: 10.1111/jne.12659] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/01/2018] [Accepted: 11/05/2018] [Indexed: 12/11/2022]
Abstract
Metabolic health founds on a homeostatic balance that has to integrate the daily changes of rest/activity and feeding/fasting cycles. A network of endogenous 24-hour circadian clocks helps to anticipate daily recurring events and adjust physiology and behavioural functions accordingly. Circadian clocks are self-sustained cellular oscillators based on a set of clock genes/proteins organised in interlocked transcriptional-translational feedback loops. The body's clocks need to be regularly reset and synchronised with each other to achieve coherent rhythmic output signals. This synchronisation is achieved by interplay of a master clock, which resides in the suprachiasmatic nucleus, and peripheral tissue clocks. This clock network is reset by time signals such as the light/dark cycle, food intake and activity. The balanced interplay of clocks is easily disturbed in modern society by shiftwork or high-energy diets, which may further promote the development of metabolic disorders. In this review, we summarise the current model of central-peripheral clock interaction in metabolic health. Different established mouse models for central or peripheral clock disruption and their metabolic phenotypes are compared and the possible relevance of clock network interaction for the development of therapeutic approaches in humans is discussed.
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Affiliation(s)
- Isa Kolbe
- Institute of Neurobiology, University of Lubeck, Lubeck, Germany
| | - Niklas Brehm
- Institute of Neurobiology, University of Lubeck, Lubeck, Germany
| | - Henrik Oster
- Institute of Neurobiology, University of Lubeck, Lubeck, Germany
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23
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Ramos-Lopez O, Samblas M, Milagro FI, Riezu-Boj JI, Crujeiras AB, Martinez JA, Project M. Circadian gene methylation profiles are associated with obesity, metabolic disturbances and carbohydrate intake. Chronobiol Int 2018; 35:969-981. [PMID: 29580070 DOI: 10.1080/07420528.2018.1446021] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 02/22/2018] [Accepted: 02/24/2018] [Indexed: 12/30/2022]
Abstract
The circadian clock regulates the daily rhythms of several physiological and behavioral processes. Disruptions in clock genes have been associated with obesity and related comorbidities. This study aimed to analyze the association of DNA methylation signatures at circadian rhythm pathway genes with body mass index (BMI), metabolic profiles and dietary intakes. DNA methylation profiling was determined by microarray in white blood cells from 474 adults from the Methyl Epigenome Network Association (MENA) project. Kyoto Encyclopedia of Genes and Genomes database was used to identify the genes integrating the circadian rhythm pathway. Network enrichment analyses were performed with the PathDIP platform. Associations between circadian methylation patterns with anthropometric measurements, the metabolic profile, clinical data and dietary intakes were analyzed. DNA methylation patterns of nine CpG sites at six circadian rhythm pathway genes were strongly correlated with BMI (false discovery rates <0.0001). These CpGs encompassed cg09578018 (RORA), cg20406576 (PRKAG2), cg10059324 (PER3), cg01180628 (BHLHE40), cg23871860 (FBXL3), cg16964728 (RORA), cg14129040 (CREB1), cg07012178 (PRKAG2) and cg24061580 (PRKAG2). Interestingly, network enrichment analyses revealed that the six BMI-associated genes statistically contributed to the regulation of the circadian rhythm pathway (p = 1.9E-10). In addition, methylation signatures at cg09578018 (RORA), cg24061580 (PRKAG2), cg01180628 (BHLHE40) and cg10059324 (PER3) also correlated with insulin resistance (p < 0.0001) and mean arterial blood pressure (p < 0.0001). Furthermore, relevant correlations (p < 0.05) between methylation at cg09578018 (RORA) and cg01180628 (BHLHE40) with total energy and carbohydrate intakes were found. This investigation revealed potential associations of DNA methylation profiles at circadian genes with obesity, metabolic disturbances and carbohydrate intake, with potential impact on weight homeostasis.
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Affiliation(s)
- Omar Ramos-Lopez
- a Department of Nutrition, Food Science and Physiology, and Center for Nutrition Research , University of Navarra , Pamplona , Spain
| | - Mirian Samblas
- a Department of Nutrition, Food Science and Physiology, and Center for Nutrition Research , University of Navarra , Pamplona , Spain
| | - Fermin I Milagro
- a Department of Nutrition, Food Science and Physiology, and Center for Nutrition Research , University of Navarra , Pamplona , Spain
- b CIBERobn , Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Carlos III Health INstitute , Madrid , Spain
| | - Jose I Riezu-Boj
- a Department of Nutrition, Food Science and Physiology, and Center for Nutrition Research , University of Navarra , Pamplona , Spain
- c Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain
| | - A B Crujeiras
- b CIBERobn , Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Carlos III Health INstitute , Madrid , Spain
- d Laboratory of Molecular and Cellular Endocrinology , Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC) , Santiago de Compostela , Spain
| | - J Alfredo Martinez
- a Department of Nutrition, Food Science and Physiology, and Center for Nutrition Research , University of Navarra , Pamplona , Spain
- b CIBERobn , Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición, Carlos III Health INstitute , Madrid , Spain
- c Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain
- e IMDEA Food , Research Institute on Food & Health Sciences , Madrid , Spain
| | - Mena Project
- f Other Members of the MENA Project in Alphabetical Order Are: Abete I, Cuervo M, Goni L, Marti A, Martinez-Gonzalez MA, Moreno-Aliaga MJ, Navas-Carretero S, San-Cristobal R, Santos JL and Zulet MA
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24
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Aryal RP, Kwak PB, Tamayo AG, Gebert M, Chiu PL, Walz T, Weitz CJ. Macromolecular Assemblies of the Mammalian Circadian Clock. Mol Cell 2017; 67:770-782.e6. [PMID: 28886335 PMCID: PMC5679067 DOI: 10.1016/j.molcel.2017.07.017] [Citation(s) in RCA: 182] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 06/14/2017] [Accepted: 07/13/2017] [Indexed: 10/18/2022]
Abstract
The mammalian circadian clock is built on a feedback loop in which PER and CRY proteins repress their own transcription. We found that in mouse liver nuclei all three PERs, both CRYs, and Casein Kinase-1δ (CK1δ) are present together in an ∼1.9-MDa repressor assembly that quantitatively incorporates its CLOCK-BMAL1 transcription factor target. Prior to incorporation, CLOCK-BMAL1 exists in an ∼750-kDa complex. Single-particle electron microscopy (EM) revealed nuclear PER complexes purified from mouse liver to be quasi-spherical ∼40-nm structures. In the cytoplasm, PERs, CRYs, and CK1δ were distributed into several complexes of ∼0.9-1.1 MDa that appear to constitute an assembly pathway regulated by GAPVD1, a cytoplasmic trafficking factor. Single-particle EM of two purified cytoplasmic PER complexes revealed ∼20-nm and ∼25-nm structures, respectively, characterized by flexibly tethered globular domains. Our results define the macromolecular assemblies comprising the circadian feedback loop and provide an initial structural view of endogenous eukaryotic clock machinery.
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Affiliation(s)
- Rajindra P Aryal
- Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Pieter Bas Kwak
- Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Alfred G Tamayo
- Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Michael Gebert
- Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Po-Lin Chiu
- Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
| | - Thomas Walz
- Laboratory of Molecular Electron Microscopy, Rockefeller University, New York, NY 10065, USA
| | - Charles J Weitz
- Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
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Kiehn JT, Tsang AH, Heyde I, Leinweber B, Kolbe I, Leliavski A, Oster H. Circadian Rhythms in Adipose Tissue Physiology. Compr Physiol 2017; 7:383-427. [PMID: 28333377 DOI: 10.1002/cphy.c160017] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The different types of adipose tissues fulfill a wide range of biological functions-from energy storage to hormone secretion and thermogenesis-many of which show pronounced variations over the course of the day. Such 24-h rhythms in physiology and behavior are coordinated by endogenous circadian clocks found in all tissues and cells, including adipocytes. At the molecular level, these clocks are based on interlocked transcriptional-translational feedback loops comprised of a set of clock genes/proteins. Tissue-specific clock-controlled transcriptional programs translate time-of-day information into physiologically relevant signals. In adipose tissues, clock gene control has been documented for adipocyte proliferation and differentiation, lipid metabolism as well as endocrine function and other adipose oscillations are under control of systemic signals tied to endocrine, neuronal, or behavioral rhythms. Circadian rhythm disruption, for example, by night shift work or through genetic alterations, is associated with changes in adipocyte metabolism and hormone secretion. At the same time, adipose metabolic state feeds back to central and peripheral clocks, adjusting behavioral and physiological rhythms. In this overview article, we summarize our current knowledge about the crosstalk between circadian clocks and energy metabolism with a focus on adipose physiology. © 2017 American Physiological Society. Compr Physiol 7:383-427, 2017.
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Affiliation(s)
- Jana-Thabea Kiehn
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Anthony H Tsang
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Isabel Heyde
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Brinja Leinweber
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Isa Kolbe
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Alexei Leliavski
- Institute of Systemic Inflammation Research, University of Lübeck, Lübeck, Germany
| | - Henrik Oster
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
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Lin E, Kuo PH, Liu YL, Yang AC, Kao CF, Tsai SJ. Effects of circadian clock genes and health-related behavior on metabolic syndrome in a Taiwanese population: Evidence from association and interaction analysis. PLoS One 2017; 12:e0173861. [PMID: 28296937 PMCID: PMC5352001 DOI: 10.1371/journal.pone.0173861] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 02/28/2017] [Indexed: 12/12/2022] Open
Abstract
Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing MetS and its individual components. A total of 3,000 Taiwanese subjects from the Taiwan Biobank were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our data showed a nominal association of MetS with several single nucleotide polymorphisms (SNPs) in five key circadian clock genes including ARNTL, GSK3B, PER3, RORA, and RORB; but none of these SNPs persisted significantly after performing Bonferroni correction. Moreover, we identified the effect of GSK3B rs2199503 on high fasting glucose (P = 0.0002). Additionally, we found interactions among the ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, RORA rs8034880, and RORB rs972902 SNPs influenced MetS (P < 0.001 ~ P = 0.002). Finally, we investigated the influence of interactions between ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, and RORB rs972902 with environmental factors such as alcohol consumption, smoking status, and physical activity on MetS and its individual components (P < 0.001 ~ P = 0.002). Our study indicates that circadian clock genes such as ARNTL, GSK3B, PER3, RORA, and RORB genes may contribute to the risk of MetS independently as well as through gene-gene and gene-environment interactions.
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Affiliation(s)
- Eugene Lin
- Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Vita Genomics, Inc., Taipei, Taiwan
- TickleFish Systems Corporation, Seattle, Western Australia, United States of America
- * E-mail: (EL); (SJT)
| | - Po-Hsiu Kuo
- Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Li Liu
- Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan
| | - Albert C. Yang
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan
| | - Chung-Feng Kao
- Department of Agronomy, College of Agriculture & Natural Resources, National Chung Hsing University, Taichung, Taiwan
| | - Shih-Jen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
- Division of Psychiatry, National Yang-Ming University, Taipei, Taiwan
- * E-mail: (EL); (SJT)
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Adhikary N, Shrestha SL, Sun JZ. Metabolic disturbances: role of the circadian timing system and sleep. Diabetol Int 2017; 8:14-22. [PMID: 30603302 PMCID: PMC6224937 DOI: 10.1007/s13340-016-0279-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 06/28/2016] [Indexed: 12/21/2022]
Abstract
The incidence of metabolic disorders such as obesity and diabetes is on the rise, and food quality is not alone to blame. Sleep disturbances, altered feeding time and circadian disruption are linked to metabolic disturbances in many clinical research studies and cross-sectional analyses. This review tried to summarize the role of the circadian timing system and sleep on energy and metabolic homeostasis. We also tried to explain the molecular and endocrine mechanisms behind circadian misalignment and sleep disorders that lead to metabolic disorders.
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Affiliation(s)
- Navin Adhikary
- Department of Endocrinology, Zhongnan Hospital, Wuhan University, Wuhan, 430071 China
| | - Santosh Lal Shrestha
- Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, 430060 China
| | - Jia Zhong Sun
- Department of Endocrinology, Zhongnan Hospital, Wuhan University, Wuhan, 430071 China
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28
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Tsang AH, Astiz M, Leinweber B, Oster H. Rodent Models for the Analysis of Tissue Clock Function in Metabolic Rhythms Research. Front Endocrinol (Lausanne) 2017; 8:27. [PMID: 28243224 PMCID: PMC5304405 DOI: 10.3389/fendo.2017.00027] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 01/30/2017] [Indexed: 11/30/2022] Open
Abstract
The circadian timing system consists on a distributed network of cellular clocks that together coordinate 24-h rhythms of physiology and behavior. Clock function and metabolism are tightly coupled, from the cellular to the organismal level. Genetic and non-genetic approaches in rodents have been employed to study circadian clock function in the living organism. Due to the ubiquitous expression of clock genes and the intricate interaction between the circadian system and energy metabolism, genetic approaches targeting specific tissue clocks have been used to assess their contribution in systemic metabolic processes. However, special requirements regarding specificity and efficiency have to be met to allow for valid conclusions from such studies. In this review, we provide a brief summary of different approaches developed for dissecting tissue clock function in the metabolic context in rodents, compare their strengths and weaknesses, and suggest new strategies in assessing tissue clock output and the consequences of circadian clock disruption in vivo.
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Affiliation(s)
- Anthony H. Tsang
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
- Department of Clinical Biochemistry, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Mariana Astiz
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Brinja Leinweber
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
| | - Henrik Oster
- Chronophysiology Group, Medical Department I, University of Lübeck, Lübeck, Germany
- *Correspondence: Henrik Oster,
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29
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Freije WA, Thamotharan S, Lee R, Shin BC, Devaskar SU. The hepatic transcriptome of young suckling and aging intrauterine growth restricted male rats. J Cell Biochem 2016; 116:566-79. [PMID: 25371150 DOI: 10.1002/jcb.25008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 10/30/2014] [Indexed: 01/20/2023]
Abstract
Intrauterine growth restriction leads to the development of adult onset obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease, hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver disease/steatohepatitis. Continued postnatal growth restriction has been shown to ameliorate many of these sequelae. To further our understanding of the mechanism of how intrauterine and early postnatal growth affects adult health we have employed Affymetrix microarray-based expression profiling to characterize hepatic gene expression of male offspring in a rat model of maternal nutrient restriction in early and late life. At day 21 of life (p21) combined intrauterine and postnatal calorie restriction treatment led to expression changes in circadian, metabolic, and insulin-like growth factor genes as part of a larger transcriptional response that encompasses 144 genes. Independent and controlled experiments at p21 confirm the early life circadian, metabolic, and growth factor perturbations. In contrast to the p21 transcriptional response, at day 450 of life (d450) only seven genes, largely uncharacterized, were differentially expressed. This lack of a transcriptional response identifies non-transcriptional mechanisms mediating the adult sequelae of intrauterine growth restriction. Independent experiments at d450 identify a circadian defect as well as validate expression changes to four of the genes identified by the microarray screen which have a novel association with growth restriction. Emerging from this rich dataset is a portrait of how the liver responds to growth restriction through circadian dysregulation, energy/substrate management, and growth factor modulation.
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Affiliation(s)
- William A Freije
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, California
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30
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Zhou D, Wang Y, Chen L, Jia L, Yuan J, Sun M, Zhang W, Wang P, Zuo J, Xu Z, Luan J. Evolving roles of circadian rhythms in liver homeostasis and pathology. Oncotarget 2016; 7:8625-39. [PMID: 26843619 PMCID: PMC4890992 DOI: 10.18632/oncotarget.7065] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
Circadian clock in mammals is determined by a core oscillator in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronized peripheral clocks in other tissues. The coherent timing systems could sustain robust output of circadian rhythms in response to the entrainment controlled environmentally. Disparate approaches have discovered that clock genes and clock-controlled genes (CCGs) exist in nearly all mammalian cell types and are essential for establishing the mechanisms and complexity of internal time-keeping systems. Accumulating evidence demonstrates that the control of homeostasis and pathology in the liver involves intricate loops of transcriptional and post-translational regulation of clock genes expression. This review will focus on the recent advances with great importance concerning clock rhythms linking liver homeostasis and diseases. We particularly highlight what is currently known of the evolving insights into the mechanisms underlying circadian clock . Eventually , findings during recent years in the field might prompt new circadian-related chronotherapeutic strategies for the diagnosis and treatment of liver diseases by coupling these processes.
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Affiliation(s)
- Dexi Zhou
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Yaqin Wang
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Lu Chen
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Leijuan Jia
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Jie Yuan
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Mei Sun
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Wen Zhang
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Peipei Wang
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Jian Zuo
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Zhenyu Xu
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Jiajie Luan
- Laboratory of Clinical Pharmacy of Wannan Medical College, Wuhu, Anhui Province, China
- Department of Pharmacy in Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
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31
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Krueger KC, Feldman BJ. Adipose circadian clocks: coordination of metabolic rhythms by clock genes, steroid hormones, and PPARs. Horm Mol Biol Clin Investig 2015; 14:15-24. [PMID: 25436716 DOI: 10.1515/hmbci-2013-0011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Accepted: 04/30/2013] [Indexed: 12/23/2022]
Abstract
A central clock consisting of interconnected positive and negative feedback gene loops operates in the brain, tying rhythmic activity to the 24-h day. The central clock entrains similar feedback loops present in most peripheral tissues to coordinate metabolic gene expression among organs and with feeding activity for more efficient utilization of resources. Recent studies are beginning to elucidate the intricate feedback mechanisms among central and peripheral clocks and their roles in activity and metabolic homeostasis. Adipose tissue serves as a major energy storage organ and releases paracrine and endocrine hormones to signal energy status to other organs. Within the adipose tissue, the transcriptional feedback regulation between clock genes and nuclear hormone receptors, together with direct protein associations among these molecules, ensures the expression of metabolic genes at the appropriate time. This review will summarize the important components and mechanisms of adipose clock entrainment, particularly highlighting instructive studies carried out in mice. This research not only illustrates the intricate connections between clocks and metabolism but also provides potential mechanisms to correct abnormalities induced by disrupted sleep or poor diet.
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Karthikeyan R, Marimuthu G, Sooriyakumar M, BaHammam AS, Spence DW, Pandi-Perumal SR, Brown GM, Cardinali DP. Per3 length polymorphism in patients with type 2 diabetes mellitus. Horm Mol Biol Clin Investig 2015; 18:145-9. [PMID: 25390010 DOI: 10.1515/hmbci-2013-0049] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Accepted: 11/14/2013] [Indexed: 11/15/2022]
Abstract
BACKGROUND A number of observations support the involvement of circadian clock genes in the regulation of metabolic processes. One of these circadian genes, Per3, exhibits a variable number tandem repeat length polymorphism, consisting of two alleles, namely four and five repeat alleles, in its exon 18. The objective of this study was to examine the existence of Per3 variants in patients with type 2 diabetes mellitus (T2DM) as compared to a non T2DM control group. METHODS Intravenous blood samples were collected to obtain white blood cells from 302 T2DM patients and 330 non-diabetic, age- and sex-matched, individuals. Per3 genotyping was performed on DNA by polymerase chain reaction. RESULTS Frequency of five repeat allele was higher, and that of four repeat allele lower, in T2DM patients as compared to non-diabetic controls (χ2=6.977, p=0.0082) CONCLUSIONS: The results indicate an association of Per3 five repeat allele with T2DM occurrence and suggest that individuals with five repeat allele may be at a greater risk for T2DM as compared to those carrying the four repeat allele.
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Abstract
The circadian clock plays an integral role in the regulation of physiological processes, including the regulation of blood pressure. However, deregulation of the clock can lead to pathophysiological states including hypertension. Recent work has implicated the circadian clock genes in the regulation of processes in the heart, kidney, vasculature, and the metabolic organs, which are all critical in the regulation of the blood pressure. The goal of this review is to provide an introduction and general overview into the role of circadian clock genes in the regulation of blood pressure with a focus on their deregulation in the etiology of hypertension. This review will focus on the core circadian clock genes CLOCK, BMAL1, Per, and Cry.
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Abstract
Circadian clocks optimize the timing of physiological processes in synchrony with daily recurring and therefore predictable changes in the environment. Until the late 1990s, circadian clocks were thought to exist only in the central nervous systems of animals; elegant studies in cultured fibroblasts and using genetically encoded reporters in Drosophila melanogaster and in mice showed that clocks are ubiquitous and cell autonomous. These findings inspired investigations of the advantages construed by enabling each organ to independently adjust its function to the time of day. Studies of rhythmic gene expression in several organs suggested that peripheral organ clocks might play an important role in optimizing metabolic physiology by synchronizing tissue-intrinsic metabolic processes to cycles of nutrient availability and energy requirements. The effects of clock disruption in liver, pancreas, muscle, and adipose tissues support that hypothesis. Adipose tissues coordinate energy storage and utilization and modulate behavior and the physiology of other organs by secreting hormones known as "adipokines." Due to behavior- and environment-driven diurnal variations in supply and demand for chemical and thermal energy, adipose tissues might represent an important peripheral location for coordinating circadian energy balance (intake, storage, and utilization) over the whole organism. Given the complexity of adipose cell types and depots, the sensitivity of adipose tissue biology to age and diet composition, and the plethora of known and yet-to-be-discovered adipokines and lipokines, we have just begun to scratch the surface of understanding the role of circadian clocks in adipose tissues.
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Affiliation(s)
- Emma Henriksson
- Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA Department of Clinical Sciences, Lund University, CRC, Malmö, Sweden
| | - Katja A Lamia
- Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA
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35
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Yamaguchi M, Kotani K, Tsuzaki K, Takagi A, Motokubota N, Komai N, Sakane N, Moritani T, Nagai N. Circadian rhythm genes CLOCK and PER3 polymorphisms and morning gastric motility in humans. PLoS One 2015; 10:e0120009. [PMID: 25775462 PMCID: PMC4388463 DOI: 10.1371/journal.pone.0120009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Accepted: 01/19/2015] [Indexed: 01/20/2023] Open
Abstract
Background Clock genes regulate circadian rhythm and are involved in various
physiological processes, including digestion. We therefore investigated the
association between the CLOCK 3111T/C single nucleotide
polymorphism and the Period3 (PER3)
variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in
length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with
173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by
electrogastrography (EGG), blood pressure, and heart rate levels were
measured at 8:30 a.m. after an overnight fast. For gastric motility, the
spectral powers (% normal power) and dominant frequency (DF, peak of the
power spectrum) of the EGG were evaluated. The CLOCK and
PER3 polymorphisms were determined by polymerase chain
reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n =
59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T
genotype (n = 114, 2.81 cpm, P < 0.05). Subjects
with the longer PER3 allele
(PER34/5 or
PER35/5 genotypes: n = 65) also showed a
significantly lower DF (2.55 cpm) than those with the shorter
PER34/4 genotype (n = 108, 2.83 cpm,
P < 0.05). Furthermore, subjects with both the
T/C or C/C and PER34/5 or
PER35/5 genotypes showed a significantly
lower DF (2.43 cpm, P < 0.05) than subjects with
other combinations of the alleles (T/T and
PER34/4 genotype, T/C or C/C and
PER34/4 genotypes, and T/T and
PER34/5 or
PER35/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes
CLOCK and PER3 may be associated with
poor morning gastric motility, and may have a combinatorial effect. The
present findings may offer a new viewpoint on the role of circadian rhythm
genes on the peripheral circadian systems, including the time-keeping
function of the gut.
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Affiliation(s)
- Mitsue Yamaguchi
- Graduate School of Human Science and Environment, University of Hyogo,
Hyogo, Japan
| | - Kazuhiko Kotani
- Department of Clinical Laboratory Medicine, Jichi Medical University,
Shimotsuke-Tochigi, Japan
- Division of Preventive Medicine, Clinical Research Institute for
Endocrine and Metabolic Disease, National Hospital Organization, Kyoto Medical
Center, Kyoto, Japan
| | - Kokoro Tsuzaki
- Division of Preventive Medicine, Clinical Research Institute for
Endocrine and Metabolic Disease, National Hospital Organization, Kyoto Medical
Center, Kyoto, Japan
| | - Ayaka Takagi
- Graduate School of Human Science and Environment, University of Hyogo,
Hyogo, Japan
| | - Naoko Motokubota
- Graduate School of Human Science and Environment, University of Hyogo,
Hyogo, Japan
| | - Naho Komai
- Graduate School of Human Science and Environment, University of Hyogo,
Hyogo, Japan
| | - Naoki Sakane
- Division of Preventive Medicine, Clinical Research Institute for
Endocrine and Metabolic Disease, National Hospital Organization, Kyoto Medical
Center, Kyoto, Japan
| | - Toshio Moritani
- Laboratory of Applied Physiology, Graduate School of Human and
Environmental Studies, Kyoto University, Kyoto, Japan
| | - Narumi Nagai
- Graduate School of Human Science and Environment, University of Hyogo,
Hyogo, Japan
- * E-mail:
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36
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Elvira AL, Caldelas I, De Ita-Pérez D, Díaz-Muñoz M. The circadian timing system: a recent addition in the physiological mechanisms underlying pathological and aging processes. Aging Dis 2014; 5:406-18. [PMID: 25489492 DOI: 10.14336/ad.2014.0500406] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2013] [Revised: 12/09/2013] [Accepted: 01/05/2014] [Indexed: 11/01/2022] Open
Abstract
Experimental findings and clinical observations have strengthened the association between physio-pathologic aspects of several diseases, as well as aging process, with the occurrence and control of circadian rhythms. The circadian system is composed by a principal pacemaker in the suprachiasmatic nucleus (SNC) which is in coordination with a number of peripheral circadian oscillators. Many pathological entities such as metabolic syndrome, cancer and cardiovascular events are strongly connected with a disruptive condition of the circadian cycle. Inadequate circadian physiology can be elicited by genetic defects (mutations in clock genes or circadian control genes) or physiological deficiencies (desynchronization between SCN and peripheral oscillators). In this review, we focus on the most recent experimental findings regarding molecular defects in the molecular circadian clock and the altered coordination in the circadian system that are related with clinical conditions such as metabolic diseases, cancer predisposition and physiological deficiencies associated to jet-lag and shiftwork schedules. Implications in the aging process will be also reviewed.
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Affiliation(s)
| | - Ivette Caldelas
- Instituto de Investigaciones Biomédicas, UNAM, Ciudad de México 04510, D.F., MÉXICO
| | - Dalia De Ita-Pérez
- Instituto de Investigaciones Biomédicas, UNAM, Ciudad de México 04510, D.F., MÉXICO
| | - Mauricio Díaz-Muñoz
- Instituto de Investigaciones Biomédicas, UNAM, Ciudad de México 04510, D.F., MÉXICO
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Yamaoka M, Maeda N, Takayama Y, Sekimoto R, Tsushima Y, Matsuda K, Mori T, Inoue K, Nishizawa H, Tominaga M, Funahashi T, Shimomura I. Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat. PLoS One 2014; 9:e112813. [PMID: 25397888 PMCID: PMC4232416 DOI: 10.1371/journal.pone.0112813] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Accepted: 10/15/2014] [Indexed: 12/12/2022] Open
Abstract
Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.
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Affiliation(s)
- Masaya Yamaoka
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Norikazu Maeda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
- * E-mail:
| | - Yasunori Takayama
- Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan
| | - Ryohei Sekimoto
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Yu Tsushima
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Keisuke Matsuda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Takuya Mori
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Kana Inoue
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Hitoshi Nishizawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Makoto Tominaga
- Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan
- Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi, 444-8585, Japan
| | - Tohru Funahashi
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
- Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
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38
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Vieira E, Burris TP, Quesada I. Clock genes, pancreatic function, and diabetes. Trends Mol Med 2014; 20:685-93. [PMID: 25457619 DOI: 10.1016/j.molmed.2014.10.007] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 10/10/2014] [Accepted: 10/14/2014] [Indexed: 11/28/2022]
Abstract
Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes.
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Affiliation(s)
- Elaine Vieira
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08033 Barcelona, Spain.
| | - Thomas P Burris
- Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO 63104, USA
| | - Ivan Quesada
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08033 Barcelona, Spain; Instituto de Bioingeniería, Universidad Miguel Hernández, 03202 Elche, Spain.
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39
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Karthikeyan R, Marimuthu G, Spence DW, Pandi-Perumal SR, BaHammam AS, Brown GM, Cardinali DP. Should we listen to our clock to prevent type 2 diabetes mellitus? Diabetes Res Clin Pract 2014; 106:182-90. [PMID: 25172521 DOI: 10.1016/j.diabres.2014.07.029] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Revised: 05/25/2014] [Accepted: 07/31/2014] [Indexed: 11/15/2022]
Abstract
The circadian clock drives a number of metabolic processes including energy intake, storage and utilization coupled with the sleep/wake cycles. Globally, the increasing prevalence of type 2 diabetes (T2DM) has become a significant international public health concern. In view of the heavy societal burden caused by diabetes, and further, to reduce its growing incidence, it is clearly essential to understand the causes of this disease and to devise more effective strategies for its treatment. Although many factors cause T2DM, this article centers on the role of circadian regulation of metabolism. The correlation between the increased occurrence of T2DM and the ubiquity of modern social pressures such as 24/7 lifestyles as well as nocturnal lighting conditions point strongly to the hypothesis that malfunctioning of circadian controls may be involved in the etiology of the illness. Nocturnal light exposure, unusual timing of food, irregular sleep/wake schedules and traveling between different time zones are some of the factors responsible for improper entrainment of the clock. Recent reports have proposed that strengthening of circadian clock functioning and proper timing of food intake could stabilize glucose homeostasis. This strategy thus represents a chronotherapeutic option for non-pharmaceutical intervention in treating T2DM patients.
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Affiliation(s)
- Ramanujam Karthikeyan
- Department of Animal Behaviour, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India
| | - Ganapathy Marimuthu
- Department of Animal Behaviour, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India.
| | | | - Seithikurippu R Pandi-Perumal
- Center for Healthful Behavior Change (CHBC), Division of Health and Behavior, Department of Population Health, New York University Medical Center, Clinical & Translational Research Institute, New York, NY 10016, USA
| | - Ahmed S BaHammam
- University Sleep Disorders Center, College of Medicine, National Plan for Science and Technology, King Saud University, Riyadh, Saudi Arabia
| | - Gregory M Brown
- Centre for Addiction and Mental Health, University of Toronto, 100 Stokes St., Toronto, ON M6J 1H4, Canada
| | - Daniel P Cardinali
- Department of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, 1107, Argentina
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40
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Abstract
Most organisms display endogenously produced ∼ 24-hour fluctuations in physiology and behavior, termed circadian rhythms. Circadian rhythms are driven by a transcriptional-translational feedback loop that is hierarchically expressed throughout the brain and body, with the suprachiasmatic nucleus of the hypothalamus serving as the master circadian oscillator at the top of the hierarchy. Appropriate circadian regulation is important for many homeostatic functions including energy regulation. Multiple genes involved in nutrient metabolism display rhythmic oscillations, and metabolically related hormones such as glucagon, insulin, ghrelin, leptin, and corticosterone are released in a circadian fashion. Mice harboring mutations in circadian clock genes alter feeding behavior, endocrine signaling, and dietary fat absorption. Moreover, misalignment between behavioral and molecular circadian clocks can result in obesity in both rodents and humans. Importantly, circadian rhythms are most potently synchronized to the external environment by light information and exposure to light at night potentially disrupts circadian system function. Since the advent of electric lights around the turn of the 20th century, exposure to artificial and irregular light schedules has become commonplace. The increase in exposure to light at night parallels the global increase in the prevalence of obesity and metabolic disorders. In this review, we propose that exposure to light at night alters metabolic function through disruption of the circadian system. We first provide an introduction to the circadian system, with a specific emphasis on the effects of light on circadian rhythms. Next we address interactions between the circadian system and metabolism. Finally, we review current experimental and epidemiological work directly associating exposure to light at night and metabolism.
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Affiliation(s)
- Laura K Fonken
- Department of Neuroscience, Wexner Medical Center, The Ohio State University, Columbus, Ohio 43210
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41
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Lipkova J, Splichal Z, Bienertova-Vasku JA, Jurajda M, Parenica J, Vasku A, Goldbergova MP. Period3VNTR polymorphism influences the time-of-day pain onset of acute myocardial infarction with ST elevation. Chronobiol Int 2014; 31:878-90. [DOI: 10.3109/07420528.2014.921790] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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42
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Ramanathan C, Xu H, Khan SK, Shen Y, Gitis PJ, Welsh DK, Hogenesch JB, Liu AC. Cell type-specific functions of period genes revealed by novel adipocyte and hepatocyte circadian clock models. PLoS Genet 2014; 10:e1004244. [PMID: 24699442 PMCID: PMC3974647 DOI: 10.1371/journal.pgen.1004244] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 02/02/2014] [Indexed: 12/02/2022] Open
Abstract
In animals, circadian rhythms in physiology and behavior result from coherent rhythmic interactions between clocks in the brain and those throughout the body. Despite the many tissue specific clocks, most understanding of the molecular core clock mechanism comes from studies of the suprachiasmatic nuclei (SCN) of the hypothalamus and a few other cell types. Here we report establishment and genetic characterization of three cell-autonomous mouse clock models: 3T3 fibroblasts, 3T3-L1 adipocytes, and MMH-D3 hepatocytes. Each model is genetically tractable and has an integrated luciferase reporter that allows for longitudinal luminescence recording of rhythmic clock gene expression using an inexpensive off-the-shelf microplate reader. To test these cellular models, we generated a library of short hairpin RNAs (shRNAs) against a panel of known clock genes and evaluated their impact on circadian rhythms. Knockdown of Bmal1, Clock, Cry1, and Cry2 each resulted in similar phenotypes in all three models, consistent with previous studies. However, we observed cell type-specific knockdown phenotypes for the Period and Rev-Erb families of clock genes. In particular, Per1 and Per2, which have strong behavioral effects in knockout mice, appear to play different roles in regulating period length and amplitude in these peripheral systems. Per3, which has relatively modest behavioral effects in knockout mice, substantially affects period length in the three cellular models and in dissociated SCN neurons. In summary, this study establishes new cell-autonomous clock models that are of particular relevance to metabolism and suitable for screening for clock modifiers, and reveals previously under-appreciated cell type-specific functions of clock genes. Various aspects of our daily rhythms in physiology and behavior such as the sleep-wake cycle are regulated by endogenous circadian clocks that are present in nearly every cell. It is generally accepted that these oscillators share a similar biochemical negative feedback mechanism, consisting of transcriptional activators and repressors. In this study, we developed cell-autonomous, metabolically relevant clock models in mouse hepatocytes and adipocytes. Each clock model has an integrated luciferase reporter that allows for kinetic luminescence recording with an inexpensive microplate reader and thus is feasible for most laboratories. These models are amenable to high throughput screening of small molecules or genomic entities for impacts on cell-autonomous clocks relevant to metabolism. We validated these new models by RNA interference via lentivirus-mediated knockdown of known clock genes. As expected, we found that many core clock components have similar functions across cell types. To our surprise, however, we also uncovered previously under-appreciated cell type-specific functions of core clock genes, particularly Per1, Per2, and Per3. Because the circadian system is integrated with, and influenced by, the local physiology that is under its control, our studies provide important implications for future studies into cell type-specific mechanisms of various circadian systems.
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Affiliation(s)
- Chidambaram Ramanathan
- Department of Biological Sciences, University of Memphis, Memphis, Tennessee, United States of America
| | - Haiyan Xu
- Department of Biological Sciences, University of Memphis, Memphis, Tennessee, United States of America
| | - Sanjoy K. Khan
- Department of Biological Sciences, University of Memphis, Memphis, Tennessee, United States of America
| | - Yang Shen
- Department of Biological Sciences, University of Memphis, Memphis, Tennessee, United States of America
| | - Paula J. Gitis
- Department of Psychiatry, University of California, San Diego, La Jolla, California, United States of America
- Center for Chronobiology, University of California, San Diego, La Jolla, California, United States of America
| | - David K. Welsh
- Department of Psychiatry, University of California, San Diego, La Jolla, California, United States of America
- Center for Chronobiology, University of California, San Diego, La Jolla, California, United States of America
- Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America
| | - John B. Hogenesch
- Department of Pharmacology and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
| | - Andrew C. Liu
- Department of Biological Sciences, University of Memphis, Memphis, Tennessee, United States of America
- Feinstone Genome Research Center, University of Memphis, Memphis, Tennessee, United States of America
- * E-mail:
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43
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Yasutake K, Kohjima M, Kotoh K, Nakashima M, Nakamuta M, Enjoji M. Dietary habits and behaviors associated with nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20:1756-67. [PMID: 24587653 PMCID: PMC3930974 DOI: 10.3748/wjg.v20.i7.1756] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Revised: 11/11/2013] [Accepted: 12/03/2013] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of health problems in Western (industrialized) countries. Moreover, the incidence of infantile NAFLD is increasing, with some of these patients progressing to nonalcoholic steatohepatitis. These trends depend on dietary habits and life-style. In particular, overeating and its associated obesity affect the development of NAFLD. Nutritional problems in patients with NAFLD include excess intake of energy, carbohydrates, and lipids, and shortages of polyunsaturated fatty acids, vitamins, and minerals. Although nutritional therapeutic approaches are required for prophylaxis and treatment of NAFLD, continuous nutrition therapy is difficult for many patients because of their dietary habits and lifestyle, and because the motivation for treatment differs among patients. Thus, it is necessary to assess the nutritional background and to identify nutritional problems in each patient with NAFLD. When assessing dietary habits, it is important to individually evaluate those that are consumed excessively or insufficiently, as well as inappropriate eating behaviors. Successful nutrition therapy requires patient education, based on assessments of individual nutrients, and continuing the treatment. In this article, we update knowledge about NAFLD, review the important aspects of nutritional assessment targeting treatment success, and present some concrete nutritional care plans which can be applied generally.
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44
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Griebel G, Ravinet-Trillou C, Beeské S, Avenet P, Pichat P. Mice deficient in cryptochrome 1 (cry1 (-/-)) exhibit resistance to obesity induced by a high-fat diet. Front Endocrinol (Lausanne) 2014; 5:49. [PMID: 24782829 PMCID: PMC3988402 DOI: 10.3389/fendo.2014.00049] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 03/26/2014] [Indexed: 12/03/2022] Open
Abstract
Disruption of circadian clock enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. Circadian clocks rely on a highly regulated network of transcriptional and translational loops that drive clock-controlled gene expression. Among these transcribed clock genes are cryptochrome (CRY) family members, which comprise Cry1 and Cry2. While the metabolic effects of deletion of several core components of the clock gene machinery have been well characterized, those of selective inactivation of Cry1 or Cry2 genes have not been described. In this study, we demonstrate that ablation of Cry1, but not Cry2, prevents high-fat diet (HFD)-induced obesity in mice. Despite similar caloric intake, Cry1 (-/-) mice on HFD gained markedly less weight (-18%) at the end of the 16-week experiment and displayed reduced fat accumulation compared to wild-type (WT) littermates (-61%), suggesting increased energy expenditure. Analysis of serum lipid and glucose profiles showed no difference between Cry1 (-/-) and WT mice. Both Cry1 (-/-) and Cry2 (-/-) mice are indistinguishable from WT controls in body weight, fat and protein contents, and food consumption when they are allowed unlimited access to a standard rodent diet. We conclude that although CRY signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, Cry1 may play a role in readjusting energy balance under changing nutritional circumstances. These studies reinforce the important role of circadian clock genes in energy homeostasis and suggest that Cry1 is a plausible target for anti-obesity therapy.
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Affiliation(s)
- Guy Griebel
- Exploratory Unit, Sanofi R&D, Chilly-Mazarin, France
- *Correspondence: Guy Griebel, Exploratory Unit, Sanofi R&D, 1 Avenue Pierre Brossolette, Chilly-Mazarin 91385, France e-mail:
| | | | - Sandra Beeské
- Exploratory Unit, Sanofi R&D, Chilly-Mazarin, France
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45
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Pollin TI, Quartuccio M. What We Know About Diet, Genes, and Dyslipidemia: Is There Potential for Translation? Curr Nutr Rep 2013; 2:236-242. [PMID: 24524012 DOI: 10.1007/s13668-013-0065-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Cardiovascular disease, particularly coronary artery disease (CAD), is the leading cause of death in the United States. Dyslipidemia, including elevated low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and low high density lipoprotein cholesterol (HDL-C), is a well-established risk factor for CAD and is influenced by both genetic and lifestyle factors, including the diet and dietary fat in particular. Major strides in elucidating the genetic basis for dyslipidemia have been made in recent years, and the quest to clarify how genetic differences influence lipid response to dietary intervention continues. Some monogenic conditions such as famililal hypercholesterolemia and sitosterolemia already have customized dietary recommendations. Some promising associations have emerged for more polygenic dyslipidemia, but further studies are needed in large dietary intervention studies capturing increasing amounts of explainable genetic variation before recommendations can be made for clinical translation.
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Affiliation(s)
- Toni I Pollin
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland ; Program in Genetics and Genomic Medicine, Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, Maryland
| | - Michael Quartuccio
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
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46
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Richards J, All S, Skopis G, Cheng KY, Compton B, Srialluri N, Stow L, Jeffers LA, Gumz ML. Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney. Am J Physiol Regul Integr Comp Physiol 2013; 305:R735-47. [PMID: 23824961 DOI: 10.1152/ajpregu.00195.2013] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Mounting evidence suggests that the circadian clock plays an integral role in the regulation of many physiological processes including blood pressure, renal function, and metabolism. The canonical molecular clock functions via activation of circadian target genes by Clock/Bmal1 and repression of Clock/Bmal1 activity by Per1-3 and Cry1/2. However, we have previously shown that Per1 activates genes important for renal sodium reabsorption, which contradicts the canonical role of Per1 as a repressor. Moreover, Per1 knockout (KO) mice exhibit a lowered blood pressure and heavier body weight phenotype similar to Clock KO mice, and opposite that of Cry1/2 KO mice. Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent mechanism, in which Per1 antagonizes Cry2, preventing its repression of Clock/Bmal1. This hypothesis was tested in vitro and in vivo. The Per1 target genes αENaC and Fxyd5 were identified as Clock targets in mpkCCDc14 cells, a model of the renal cortical collecting duct. We identified PPARα and DEC1 as novel Per1 targets in the mouse hepatocyte cell line, AML12, and in the liver in vivo. Per1 knockdown resulted in upregulation of Cry2 in vitro, and this result was confirmed in vivo in mice with reduced expression of Per1. Importantly, siRNA-mediated knockdown of Cry2 and Per1 demonstrated opposing actions for Cry2 and Per1 on Per1 target genes, supporting the potential Cry2-Clock/Bmal1-dependent mechanism underlying Per1 action in the liver and kidney.
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Affiliation(s)
- Jacob Richards
- Department of Medicine, University of Florida, Gainesville, Florida; and
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47
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Yang SC, Tseng HL, Shieh KR. Circadian-clock system in mouse liver affected by insulin resistance. Chronobiol Int 2013; 30:796-810. [DOI: 10.3109/07420528.2013.766204] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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48
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49
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Barclay JL, Shostak A, Leliavski A, Tsang AH, Jöhren O, Müller-Fielitz H, Landgraf D, Naujokat N, van der Horst GTJ, Oster H. High-fat diet-induced hyperinsulinemia and tissue-specific insulin resistance in Cry-deficient mice. Am J Physiol Endocrinol Metab 2013; 304:E1053-63. [PMID: 23531614 DOI: 10.1152/ajpendo.00512.2012] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Perturbation of circadian rhythmicity in mammals, either by environmental influences such as shiftwork or by genetic manipulation, has been associated with metabolic disturbance and the development of obesity and diabetes. Circadian clocks are based on transcriptional/translational feedback loops, comprising positive and negative components. Whereas the metabolic effects of deletion of the positive arm of the clock gene machinery, as in Clock- or Bmal1-deficient mice, have been well characterized, inactivation of Period genes (Per1-3) as components of the negative arm have more complex, sometimes contradictory effects on energy homeostasis. The CRYPTOCHROMEs are critical interaction partners of PERs, and simultaneous deletion of Cry1 and -2 results in behavioral and molecular circadian arrhythmicity. We show that, when challenged with a high-fat diet, Cry1/2(-/-) mice rapidly gain weight and surpass that of wild-type mice, despite displaying hypophagia. Transcript analysis of white adipose tissue reveals upregulated expression of lipogenic genes, many of which are insulin targets. High-fat diet-induced hyperinsulinemia, as a result of potentiated insulin secretion, coupled with selective insulin sensitivity in adipose tissue of Cry1/2(-/-) mice, correlates with increased lipid uptake. Collectively, these data indicate that Cry deficiency results in an increased vulnerability to high-fat diet-induced obesity that might be mediated by increased insulin secretion and lipid storage in adipose tissues.
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Affiliation(s)
- Johanna L Barclay
- Circadian Rhythms Group, Max Planck Institute of Biophysical Chemistry, Göttingen, Germany
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The nutrigenomic investigation of C57BL/6N mice fed a short-term high-fat diet highlights early changes in clock genes expression. GENES AND NUTRITION 2013; 8:465-74. [PMID: 23588623 DOI: 10.1007/s12263-013-0344-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 03/27/2013] [Indexed: 01/04/2023]
Abstract
Mice fed long-term high-fat diets (HFD) are an established model for human metabolic disorders, such as obesity and diabetes. However, also the effects of short-term HFD feeding should be investigated to understand which are the first events that trigger the onset of a pre-disease condition, the so-called metabolic syndrome, that increases the risk of developing clinical diseases. In this study, C57BL/6N mice were fed a control diet (CTR) or a HFD for 1 (T1) or 2 weeks (T2). Metabolic and histological effects were examined. Cecum transcriptomes of HFD and CTR mice were compared at T2 by microarray analysis. Differentially expressed genes were validated by real-time PCR in the cecum and in the liver. After 2 weeks of diet administration, HFD mice showed an altered expression pattern in only seven genes, four of which are involved in the circadian clock regulatory pathway. Real-time PCR confirmed microarray results of the cecum and revealed the same trend of clock gene expression changes in the liver. These findings suggest that clock genes may play an important role in early controlling gut output systems in response to HFD in mice and that their expression change may also represent an early signaling of the development of an intestinal pro-inflammatory status.
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