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      Feeding Rhythms and the Circadian Regulation of Metabolism

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          Abstract

          The molecular circadian clock regulates metabolic processes within the cell, and the alignment of these clocks between tissues is essential for the maintenance of metabolic homeostasis. The possibility of misalignment arises from the differential responsiveness of tissues to the environmental cues that synchronize the clock (zeitgebers). Although light is the dominant environmental cue for the master clock of the suprachiasmatic nucleus, many other tissues are sensitive to feeding and fasting. When rhythms of feeding behavior are altered, for example by shift work or the constant availability of highly palatable foods, strong feedback is sent to the peripheral molecular clocks. Varying degrees of phase shift can cause the systemic misalignment of metabolic processes. Moreover, when there is a misalignment between the endogenous rhythms in physiology and environmental inputs, such as feeding during the inactive phase, the body's ability to maintain homeostasis is impaired. The loss of phase coordination between the organism and environment, as well as internal misalignment between tissues, can produce cardiometabolic disease as a consequence. The aim of this review is to synthesize the work on the mechanisms and metabolic effects of circadian misalignment. The timing of food intake is highlighted as a powerful environmental cue with the potential to destroy or restore the synchrony of circadian rhythms in metabolism.

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          Most cited references191

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          Transcriptional architecture of the mammalian circadian clock

          Next-generation sequencing approaches have yielded new insights into circadian function. Here, Takahashi reviews genome-wide analyses of the clock transcriptional feedback loop in mammals, which reveal a global circadian regulation of transcription factor occupancy, RNA polymerase II recruitment and initiation, nascent transcription and chromatin remodelling.
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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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              Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.

              While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                17 April 2020
                2020
                : 7
                : 39
                Affiliations
                [1] 1Translational Medicine Program, The Hospital for Sick Children , Toronto, ON, Canada
                [2] 2Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, ON, Canada
                Author notes

                Edited by: Tatiana Zilberter, Independent Researcher, Marseille, France

                Reviewed by: Rebecca Anne Dumbell, Medical Research Council, United Kingdom; Gisela Helfer, University of Bradford, United Kingdom

                *Correspondence: Hoon-Ki Sung hoon-ki.sung@ 123456sickkids.ca

                This article was submitted to Neuroenergetics, Nutrition and Brain Health, a section of the journal Frontiers in Nutrition

                Article
                10.3389/fnut.2020.00039
                7182033
                32363197
                149e6f69-c2f0-4da9-b45e-3849dffc720b
                Copyright © 2020 Pickel and Sung.

                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) and the copyright owner(s) 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
                : 12 December 2019
                : 20 March 2020
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 188, Pages: 20, Words: 17289
                Funding
                Funded by: Canadian Institutes of Health Research 10.13039/501100000024
                Funded by: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada 10.13039/501100002790
                Categories
                Nutrition
                Review

                circadian,metabolism,time-restricted feeding,fasting,high fat diet,ketogenic diet,peripheral clock

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