Circadian timing of metabolism in animal models and humans

Dibner, Charna; Schibler, Ulrich

doi:10.1111/joim.12347

Cited by 207 publications

(172 citation statements)

References 156 publications

(205 reference statements)

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“…The fundamental mechanism of the mammalian circadian clock is conserved beyond the species (32). Similar mechanism may function in human cells during oncogenic transformation associated with the disruption of circadian clock machinery.…”

Section: Discussionmentioning

confidence: 99%

Different Roles of Negative and Positive Components of the Circadian Clock in Oncogene-induced Neoplastic Transformation

Katamune

Koyanagi

Shiromizu

et al. 2016

Journal of Biological Chemistry

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In mammals, circadian rhythms in physiological function are generated by a molecular oscillator driven by transcriptionaltranslational feedback loop consisting of negative and positive regulators. Disruption of this circadian clock machinery is thought to increase the risk of cancer development, but the potential contributions of each component of circadian clock to oncogenesis have been little explored. Here we reported that negative and positive transcriptional regulators of circadian feedback loop had different roles in oncogene-induced neoplastic transformation. Mouse embryonic fibroblasts prepared from animals deficient in negative circadian clock regulators, Period2 (Per2) or Cryptochrome1/2 (Cry1/2), were prone to transformation induced by co-expression of H-ras V12 and SV40 large T antigen (SV40LT). In contrast, mouse embryonic fibroblasts prepared from mice deficient in positive circadian clock regulators, Bmal1 or Clock, showed resistance to oncogene-induced transformation. In Per2 mutant and Cry1/2-null cells, the introduction of oncogenes induced expression of ATF4, a potent repressor of cell senescence-associated proteins p16INK4a and p19ARF. Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation. Conversely, in Bmal1-null and Clock mutant cells, the expression of ATF4 was not induced by oncogene introduction, which allowed constitutive expression of p16INK4a and p19ARF triggering cellular senescence. Although genetic ablation of either negative or positive transcriptional regulators of the circadian clock leads to disrupted rhythms in physiological functions, our findings define their different contributions to neoplastic cellular transformation.

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Section: Discussionmentioning

confidence: 99%

Different Roles of Negative and Positive Components of the Circadian Clock in Oncogene-induced Neoplastic Transformation

Katamune

Koyanagi

Shiromizu

et al. 2016

Journal of Biological Chemistry

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“…Fasting-feeding and rest-activity cycles are major timing cues in the synchronization of peripheral clocks (24). The SCN molecular clock communicates with peripheral tissues, such as skeletal muscle, using neurohumoral, metabolic, and temperature signals (49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

“…Fasting-feeding cycles accompanying rest-activity rhythms represent major timing cues in the synchronization of peripheral clocks (24). However, whether lipids in peripheral tissues oscillate in a cellautonomous manner has not yet been resolved.…”

Section: Significancementioning

confidence: 99%

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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“…As a consequence, most aspects of their physiology are orchestrated in a rhythmic way by the circadian clock (from the Latin circa diem, meaning "about a day"), an endogenous and autonomous oscillator with a period of around 24 h (1, 2). Not surprisingly, perturbations of this clock in mammals lead to pathologies including psychiatric, metabolic, and vascular disorders (1,3,4). At the organismal scale, the oscillatory clockwork is organized in a hierarchal manner.…”

mentioning

confidence: 99%

“…At the organismal scale, the oscillatory clockwork is organized in a hierarchal manner. Within the suprachiasmatic nuclei (SCN) of the hypothalamus, the "master clock" receives light input via the retina and communicates timing signals to "enslave" oscillators in peripheral organs (1,2). The molecular oscillator consists of interconnected transcriptional and translational feedback loops, in which multiple layers of control, including temporal posttranscriptional and posttranslational regulation, play important roles (5).…”

mentioning

confidence: 99%

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Atger

Gobet

Marquis

et al. 2015

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

212

287

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Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.circadian rhythms | ribosome profiling | mRNA translation | 5′-TOP sequences | TISU motifs L iving organisms on Earth are subjected to light-dark cycles caused by rotation of the Earth around the sun. To anticipate these changes, virtually all organisms have acquired a circadian timing system during evolution that allows a better adaptation to their environment. As a consequence, most aspects of their physiology are orchestrated in a rhythmic way by the circadian clock (from the Latin circa diem, meaning "about a day"), an endogenous and autonomous oscillator with a period of around 24 h (1, 2). Not surprisingly, perturbations of this clock in mammals lead to pathologies including psychiatric, metabolic, and vascular disorders (1,3,4). At the organismal scale, the oscillatory clockwork is organized in a hierarchal manner. Within the suprachiasmatic nuclei (SCN) of the hypothalamus, the "master clock" receives light input via the retina and communicates timing signals to "enslave" oscillators in peripheral organs (1, 2). The molecular oscillator consists of interconnected transcriptional and translational feedback loops, in which multiple layers of control, including temporal posttranscriptional and posttranslational regulation, play important roles (5). These additional layers of regulation are largely coordinated by systemic cues originating from circadian clock and/or feeding-coordinated rhythmic metabolism, allowing the adjustment of the molecular clo...

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Circadian timing of metabolism in animal models and humans

Abstract: Abstract. Dibner C, Schibler

Cited by 207 publications

References 156 publications

Different Roles of Negative and Positive Components of the Circadian Clock in Oncogene-induced Neoplastic Transformation

Different Roles of Negative and Positive Components of the Circadian Clock in Oncogene-induced Neoplastic Transformation

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

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

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