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      Circadian and Metabolic Effects of Light: Implications in Weight Homeostasis and Health

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          Abstract

          Daily interactions between the hypothalamic circadian clock at the suprachiasmatic nucleus (SCN) and peripheral circadian oscillators regulate physiology and metabolism to set temporal variations in homeostatic regulation. Phase coherence of these circadian oscillators is achieved by the entrainment of the SCN to the environmental 24-h light:dark (LD) cycle, coupled through downstream neural, neuroendocrine, and autonomic outputs. The SCN coordinate activity and feeding rhythms, thus setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism. In this work, we will discuss evidences exploring the impact of different photic entrainment conditions on energy metabolism. The steady-state interaction between the LD cycle and the SCN is essential for health and wellbeing, as its chronic misalignment disrupts the circadian organization at different levels. For instance, in nocturnal rodents, non-24 h protocols (i.e., LD cycles of different durations, or chronic jet-lag simulations) might generate forced desynchronization of oscillators from the behavioral to the metabolic level. Even seemingly subtle photic manipulations, as the exposure to a “dim light” scotophase, might lead to similar alterations. The daily amount of light integrated by the clock (i.e., the photophase duration) strongly regulates energy metabolism in photoperiodic species. Removing LD cycles under either constant light or darkness, which are routine protocols in chronobiology, can also affect metabolism, and the same happens with disrupted LD cycles (like shiftwork of jetlag) and artificial light at night in humans. A profound knowledge of the photic and metabolic inputs to the clock, as well as its endocrine and autonomic outputs to peripheral oscillators driving energy metabolism, will help us to understand and alleviate circadian health alterations including cardiometabolic diseases, diabetes, and obesity.

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          Coordinated transcription of key pathways in the mouse by the circadian clock.

          In mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed approximately 650 cycling transcripts and showed that the majority of these were specific to either the SCN or the liver. Genetic and genomic analysis suggests that a relatively small number of output genes are directly regulated by core oscillator components. Major processes regulated by the SCN and liver were found to be under circadian regulation. Importantly, rate-limiting steps in these various pathways were key sites of circadian control, highlighting the fundamental role that circadian clocks play in cellular and organismal physiology.
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            The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator.

            Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components of the general feedback loop. Thus, REV-ERBalpha constitutes a molecular link through which components of the negative limb drive antiphasic expression of components of the positive limb. While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation.
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              Molecular architecture of the mammalian circadian clock.

              Circadian clocks coordinate physiology and behavior with the 24h solar day to provide temporal homeostasis with the external environment. The molecular clocks that drive these intrinsic rhythmic changes are based on interlocked transcription/translation feedback loops that integrate with diverse environmental and metabolic stimuli to generate internal 24h timing. In this review we highlight recent advances in our understanding of the core molecular clock and how it utilizes diverse transcriptional and post-transcriptional mechanisms to impart temporal control onto mammalian physiology. Understanding the way in which biological rhythms are generated throughout the body may provide avenues for temporally directed therapeutics to improve health and prevent disease. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/456405
                URI : http://frontiersin.org/people/u/485423
                URI : http://frontiersin.org/people/u/21078
                URI : http://frontiersin.org/people/u/418172
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                19 October 2017
                2017
                : 8
                : 558
                Affiliations
                [1] 1Chronophysiology Laboratory, Institute for Biomedical Research (BIOMED – CONICET), School of Medical Sciences, Universidad Católica Argentina (UCA) , Buenos Aires, Argentina
                [2] 2Laboratorio de Cronobiología, Universidad Nacional de Quilmes – CONICET , Buenos Aires, Argentina
                Author notes

                Edited by: Ahmed S. BaHammam, King Saud University, Saudi Arabia

                Reviewed by: Timo Partonen, National Institute for Health and Welfare, Finland; Rhiannan Hope Williams, Helmholtz Zentrum München (HZ), Germany

                *Correspondence: Juan J. Chiesa, juan.chiesa@ 123456unq.edu.ar

                Specialty section: This article was submitted to Sleep and Chronobiology, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2017.00558
                5653694
                29097992
                6e104243-9d12-4411-b403-cd89aa2d6e60
                Copyright © 2017 Plano, Casiraghi, García Moro, Paladino, Golombek and Chiesa.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 June 2017
                : 04 October 2017
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 241, Pages: 21, Words: 18477
                Funding
                Funded by: Consejo Nacional de Investigaciones Científicas y Técnicas 10.13039/501100003033
                Funded by: Ministerio de Ciencia, Tecnología e Innovación Productiva 10.13039/501100002923
                Categories
                Neuroscience
                Review

                Neurology
                photic entrainment,suprachiasmatic nucleus,metabolism,desynchronization,obesity
                Neurology
                photic entrainment, suprachiasmatic nucleus, metabolism, desynchronization, obesity

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