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Molecular Insights in Circadian Rhythm and Metabolism

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (20 May 2024) | Viewed by 3463

Special Issue Editor


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Guest Editor
School of Sport and Health Sciences, University of Central Lancashire, Preston PR1 2HE, UK
Interests: metabolic syndrome; insulin resistance; obesity; tyep-2 diabetes; metabolic inflammation; chrononutrition; molecular nutrition
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Special Issue Information

Dear Colleagues,

The circadian clock coordinates biochemical, physiological, and behavioural processes in every living organism. As Albert Einstein said, "The only reason for time is so that everything does not happen at once". The internal timekeeping mechanisms operate at the cell, organ/tissue and organism levels to ensure temporal separation of the molecular events.

An essential outcome of the circadian regulatory process is achieving cellular synchrony that influences the collective outcome of the cellular response. The cellular response to a variety of stimuli is more efficient in a population of synchronized than asynchronized cells. It may be hypothesized that any inefficiency in managing oxidative stresses and inflammatory responses, the two hallmarks of most non-communicable diseases, underlies the phenomenon of cellular asynchrony.

The mammalian circadian clock’s three distinct hierarchical levels (the central clock in the suprachiasmatic center, the peripheral clocks of organs/tissues and the clock gene system at the cell level) enable constant interaction with the environmental cues (zeitgebers). While the role of photic zeitgebers in setting the biological rhythm has been widely investigated, non-photic zeitgebers, particularly the dietary ingredients (nutrients and non-nutrients), have just started to be researched.

Dietary polyphenols are powerful zeitgebers that can directly influence the circadian clock system (regulation of the clock genes) and/or indirectly (via gut microflora). Understanding the bi-directional interaction between dietary ingredients and central and peripheral clocks and clock genes may pave the way for developing novel strategies for preventing, managing, and treating non-communicable diseases.

This Special Issue of the International Journal of Molecular Sciences will showcase original research on the regulation of the mammalian circadian clock using various zeitgebers, including dietary bioactive molecules in the context of non-communicable disease models.

Topics of interest to this Special Issue include, but are not limited to, the following:

  1. The interaction of the master clock, peripheral clock and clock genes with the nutrient and non-nutrient bioactive molecules;
  2. Nutraceuticals (polyphenols), the metabolites and gut microbiome in the regulation of the circadian clock system, cellular synchrony and molecular entrainment;
  3. Regulation of cell synchrony in different biological models by various stimuli including hormonal (melatonin, cortisol), nutritional, xenobiotics, drugs, toxins, etc.;
  4. Molecular pathways of clock gene in energy homeostasis, satiety and hunger-energy mechanisms, insulin resistance and diabetes, neurodegenerative diseases, aging and cancers;
  5. Biomarkers for the assessment of the state of circadian rhythm at the three hierarchical levels.

In addition, review articles on the exploration of pharmacological and nutritional approaches targeting the circadian clock for the prevention and treatment of non-communicable diseases are also welcomed.

Dr. Bojlul Bahar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • circadian clock
  • cell synchrony
  • bioactive
  • polyphenol
  • oxidative stress
  • metabolic syndrome

Published Papers (3 papers)

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Research

16 pages, 2371 KiB  
Article
Diel Cycle Proteomics: Illuminating Molecular Dynamics in Purple Bacteria for Optimized Biotechnological Applications
by Sabine Matallana-Surget, Augustin Geron, Corentin Decroo and Ruddy Wattiez
Int. J. Mol. Sci. 2024, 25(5), 2934; https://doi.org/10.3390/ijms25052934 - 2 Mar 2024
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Abstract
Circadian rhythms, characterized by approximately 24 h cycles, play a pivotal role in enabling various organisms to synchronize their biological activities with daily variations. While ubiquitous in Eukaryotes, circadian clocks remain exclusively characterized in Cyanobacteria among Prokaryotes. These rhythms are regulated by a [...] Read more.
Circadian rhythms, characterized by approximately 24 h cycles, play a pivotal role in enabling various organisms to synchronize their biological activities with daily variations. While ubiquitous in Eukaryotes, circadian clocks remain exclusively characterized in Cyanobacteria among Prokaryotes. These rhythms are regulated by a core oscillator, which is controlled by a cluster of three genes: kaiA, kaiB, and kaiC. Interestingly, recent studies revealed rhythmic activities, potentially tied to a circadian clock, in other Prokaryotes, including purple bacteria such as Rhodospirillum rubrum, known for its applications in fuel and plastic bioproduction. However, the pivotal question of how light and dark cycles influence protein dynamics and the expression of putative circadian clock genes remains unexplored in purple non-sulfur bacteria. Unraveling the regulation of these molecular clocks holds the key to unlocking optimal conditions for harnessing the biotechnological potential of R. rubrum. Understanding how its proteome responds to different light regimes—whether under continuous light or alternating light and dark cycles—could pave the way for precisely fine-tuning bioproduction processes. Here, we report for the first time the expressed proteome of R. rubrum grown under continuous light versus light and dark cycle conditions using a shotgun proteomic analysis. In addition, we measured the impact of light regimes on the expression of four putative circadian clock genes (kaiB1, kaiB2, kaiC1, kaiC2) at the transcriptional and translational levels using RT-qPCR and targeted proteomic (MRM-MS), respectively. The data revealed significant effects of light conditions on the overall differential regulation of the proteome, particularly during the early growth stages. Notably, several proteins were found to be differentially regulated during the light or dark period, thus impacting crucial biological processes such as energy conversion pathways and the general stress response. Furthermore, our study unveiled distinct regulation of the four kai genes at both the mRNA and protein levels in response to varying light conditions. Deciphering the impact of the diel cycle on purple bacteria not only enhances our understanding of their ecology but also holds promise for optimizing their applications in biotechnology, providing valuable insights into the origin and evolution of prokaryotic clock mechanisms. Full article
(This article belongs to the Special Issue Molecular Insights in Circadian Rhythm and Metabolism)
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14 pages, 2502 KiB  
Article
Functional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures
by Hana Cho, Ahee Yun, Joohee Kim, Eunjeong Park, Jong-Wha Jung, Sooyoung Chung and Gi Hoon Son
Int. J. Mol. Sci. 2024, 25(2), 770; https://doi.org/10.3390/ijms25020770 - 7 Jan 2024
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Abstract
REV-ERBα and its paralog, REV-ERBβ, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can [...] Read more.
REV-ERBα and its paralog, REV-ERBβ, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes are controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provide strong evidence for isoform-dependent actions. For example, REV-ERBα is more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components requires REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators can help treat metabolic disturbances and certain types of cancer. Full article
(This article belongs to the Special Issue Molecular Insights in Circadian Rhythm and Metabolism)
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15 pages, 3242 KiB  
Article
Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway
by Nuria Saiz, Cristina Velasco, Nuria de Pedro, José Luis Soengas and Esther Isorna
Int. J. Mol. Sci. 2023, 24(15), 11897; https://doi.org/10.3390/ijms241511897 - 25 Jul 2023
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Abstract
The liver circadian clock plays a pivotal role in driving metabolic rhythms, being primarily entrained by the feeding schedule, although the underlying mechanisms remain elusive. This study aimed to investigate the potential role of insulin as an intake signal mediating liver entrainment in [...] Read more.
The liver circadian clock plays a pivotal role in driving metabolic rhythms, being primarily entrained by the feeding schedule, although the underlying mechanisms remain elusive. This study aimed to investigate the potential role of insulin as an intake signal mediating liver entrainment in fish. To achieve this, the expression of clock genes, which form the molecular basis of endogenous oscillators, was analyzed in goldfish liver explants treated with insulin. The presence of insulin directly increased the abundance of per1a and per2 transcripts in the liver. The dependency of protein translation for such insulin effects was evaluated using cycloheximide, which revealed that intermediate protein translation is seemingly unnecessary for the observed insulin actions. Furthermore, the putative interaction between insulin and glucocorticoid signaling in the liver was examined, with the results suggesting that both hormones exert their effects by independent mechanisms. Finally, to investigate the specific pathways involved in the insulin effects, inhibitors targeting PI3K/AKT and MEK/ERK were employed. Notably, inhibition of PI3K/AKT pathway prevented the induction of per genes by insulin, supporting its involvement in this process. Together, these findings suggest a role of insulin in fish as a key element of the multifactorial system that entrains the liver clock to the feeding schedule. Full article
(This article belongs to the Special Issue Molecular Insights in Circadian Rhythm and Metabolism)
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