Coupling governs entrainment range of circadian clocks

Abraham, Ute; Granada, Adrián E.; Westermark, Pål O.; Heine, Markus; Kramer, Achim; Herzel, Hanspeter

doi:10.1038/msb.2010.92

Cited by 320 publications

(503 citation statements)

References 85 publications

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“…The SCN molecular clock communicates with peripheral tissues, such as skeletal muscle, using neurohumoral, metabolic, and temperature signals (49)(50)(51). In our in vivo study, core clock alignment was demonstrated by plasma cortisol and melatonin profiles, as well as by muscle core clock gene expression (Fig.…”

Section: Discussionmentioning

confidence: 59%

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

Loizides‐Mangold

Perrin

Vandereycken

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest-activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophospholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlated with transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.lipid metabolism | circadian clock | human skeletal muscle | human primary myotubes | lipidomics C ircadian oscillations are daily cycles in behavior and physiology that are driven by the existence of underlying intrinsic biological clocks with near 24-h periods. This anticipatory mechanism has evolved to ensure that all aspects of behavior and physiology, including metabolic pathways, are temporally coordinated with daily cycles of rest-activity and feeding to provide the organism with an adaptive advantage (1). In mammals, circadian oscillations are driven by a master pacemaker, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which orchestrates subsidiary oscillators in peripheral organs via neuronal, endocrine, and metabolic signaling pathways (2, 3).Large-scale gene expression datasets suggest that, in mammals, the vast majority of circadian-gene expression is highly organ-specific (4-6). Key metabolic functions in peripheral organs are subject to daily oscillations, such as carbohydrate and lipid metabolism by the liver, skeletal muscle, and endocrine pancreas (7).Skeletal muscle is a major contributor of whole-body metabolism and is the main site of glucose uptake in the postprandial state (8). Therefore, perturbations in glucose sensing and metabolism in skeletal muscle are strongly associated with insulin resistance in type 2 diabetes (T2D) (9). Recent data support a fundamental role for the circadian muscle clock in the regulation of glucose uptake, with a significant re...

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Section: Discussionmentioning

confidence: 59%

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

Loizides‐Mangold

Perrin

Vandereycken

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Figure 1 shows a schematic state diagram of self-sustained oscillators. Arnold tongues of circadian clock models such as the Poincaré or the Gonze oscillator [32] can be found in references [30,33] and [34], respectively. Some of the desynchronized oscillatory dynamics illustrated in figure 1 have been observed in a variety of organisms under the respective conditions [35].…”

Section: The Periodically Forced Oscillatormentioning

confidence: 99%

Genetic redundancy strengthens the circadian clock leading to a narrow entrainment range

Erzberger

Hampp

Granada

et al. 2013

J. R. Soc. Interface.

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Circadian clocks are internal timekeepers present in almost all organisms. Driven by a genetic network of highly conserved structure, they generate selfsustained oscillations that entrain to periodic external signals such as the 24 h light-dark cycle. Vertebrates possess multiple, functionally overlapping homologues of the core clock genes. Furthermore, vertebrate clocks entrain to a range of periods three times as narrow as that of other organisms. We asked whether genetic redundancies play a role in governing entrainment properties and analysed locomotor activity rhythms of genetically modified mice lacking one set of clock homologues. Exposing them to non-24 h light-dark cycles, we found that the mutant mice have a wider entrainment range than the wild types. Spectral analysis furthermore revealed nonlinear phenomena of periodically forced self-sustained oscillators for which the entrainment range relates inversely to oscillator amplitude. Using the forced oscillator model to explain the observed differences in entrainment range between mutant and wild-type mice, we sought to quantify the overall oscillator amplitude of their clocks from the activity rhythms and found that mutant mice have weaker circadian clocks than wild types. Our results suggest that genetic redundancy strengthens the circadian clock leading to a narrow entrainment range in vertebrates.

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“…7 Ancak; fibroblast, karaciğer, böbrek ve akciğeri kapsayan periferal osilatör-ler sıcaklık değişimine oldukça hassastır. 23 J Je et t--L La ag g; farklı zaman bölgeleri arasındaki seyahati tanımlar. Yolculuk sonucu iç saat ile varış yerindeki aydınlık/karanlık döngüsü arasındaki uyuşmazlık birtakım sorunlara yol açabilmektedir.…”

Section: Si̇rkadi̇yen Ri̇tmi̇n Transkri̇psi̇yonel Ve Translasyonel Mekani̇zmasiunclassified

Circadian Rhythm, Health and Nutrition Relationship: Review

Sözlü¹,

Şanlıer²

2017

Turkiye Klinikleri J Health Sci

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Coupling governs entrainment range of circadian clocks

Cited by 320 publications

References 85 publications

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

Genetic redundancy strengthens the circadian clock leading to a narrow entrainment range

Circadian Rhythm, Health and Nutrition Relationship: Review

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