Insulin/IGF-1 Drives PERIOD Synthesis to Entrain Circadian Rhythms with Feeding Time

Crosby, Priya; Hamnett, Ryan; Putker, Marrit; Hoyle, Nathaniel P.; Reed, Martin; Karam, Carolyn J.; Maywood, Elizabeth S.; Stangherlin, Alessandra; Chesham, Johanna E.; Hayter, Edward A; Rosenbrier-Ribeiro, Lyn; Newham, Peter; Clevers, Hans; Bechtold, David A.; O’Neill, John S.

doi:10.1016/j.cell.2019.02.017

Cited by 256 publications

(233 citation statements)

References 91 publications

(125 reference statements)

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“…Circadian rhythms regulate CCGs in a tissue-specific manner throughout the body 53 . Circadian rhythms in peripheral organs are affected by numerous inputs including light 54,55 , nutrients 22,56,57 , and systemic cues from SCN [58][59][60][61][62] . Previous studies characterizing CCGs in different organs from in vivo mice uncovered organ-specific regulation of circadian rhythms integrated by both peripheral clocks and systemic cues from SCN.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny and function of the circadian clock in intestinal organoids

Rosselot

Park

Matsuura

et al. 2020

Preprint

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Circadian rhythms regulate diverse aspects of gastrointestinal physiology ranging from the composition of microbiota to motility. However, development of the intestinal circadian clock and detailed molecular mechanisms regulating circadian physiology of the intestine remain largely unknown. The lack of appropriate human model systems that enable organ-and/or diseasespecific interrogation of clock functions is a major obstacle hindering advancements of translational applications using chronotherapy. In this report, we show that both pluripotent stem cell-derived human intestinal organoids engrafted into mice and patient-derived human intestinal enteroids (HIEs) possess robust circadian rhythms, and demonstrate circadian phase-dependent necrotic cell death responses to Clostridium difficile toxin B (TcdB). Intriguingly, mouse and human enteroids demonstrate anti-phasic necrotic cell death responses. RNA-Seq data show ~4% of genes are rhythmically expressed in HIEs. Remarkably, we observe anti-phasic gene expression of Rac1, a small GTPase directly inactivated by TcdB, between mouse and human enteroids. Importantly, the observed circadian time-dependent necrotic cell death response is abolished in both mouse enteroids and human intestinal organoids (HIOs) lacking robust circadian rhythms. Our findings uncover robust functions of circadian rhythms regulating critical clockcontrolled genes (CCGs) in human enteroids governing organism-specific, circadian phasedependent necrotic cell death responses. Our data highlight unique differences between mouse and human enteroids, and lay a foundation for human organ-and disease-specific investigation of clock functions using human organoids for translational applications.

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Section: Discussionmentioning

confidence: 99%

Ontogeny and function of the circadian clock in intestinal organoids

Rosselot

Park

Matsuura

et al. 2020

Preprint

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“…Thus, it is unlikely that its circadian rhythm will dictate IGF-I signaling to orexin neurons. Rather, it seems more plausible that brain and physical activity 24,25 , and/or feeding schedule 26 will modulate orexin activity, since all these situations are accompanied by increased brain IGF-I input. But more work is needed to determine the specific cues timing IGF-I input to orexin neurons.…”

Section: Discussionmentioning

confidence: 99%

“…ECG segments of 5 minutes were analyzed with this software using the Fast Fourier Transform algorithm to obtain the power spectra. The mean power density was calculated for 5 different frequency bands that constitute the global ECG: delta band (0.3-5 Hz), theta band (5-8 Hz), alpha band (8-12 Hz), beta band (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Hz), and gamma band . The total power of the five frequency bands was considered 100%, and the percentage of each frequency band was calculated for the 60 minutes.…”

Section: Electrocorticogram (Ecg) Recordings In Freely Moving Animalsmentioning

confidence: 99%

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Insulin-Like Growth Factor I Modulates Sleep Through Hypothalamic Orexin Neurons

Zegarra-Valdivia

Pignatelli

Sevilla

et al. 2020

Preprint

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Although metabolic and sleep disturbances are commonly associated, the underlying processes are not yet fully defined. Insulin-like growth factor-I (IGF-I), an anabolic hormone that shows a circadian pattern in the circulation, is associated to sleep regulation along evolution. However, its role in this universal homeostatic process remains poorly understood. We now report that the activity of orexin neurons, a discrete cell population in the lateral hypothalamus that is involved in the circadian sleep/wake cycle, is modulated by circulating IGF-I. Furthermore, mice with blunted IGF-I receptor activity in orexin neurons have lower levels of orexin in the hypothalamus, show altered electrocorticographic patterns with predominant slow wave activity, reduced onset-sleep latency, and less transitions between sleep and awake stages. Collectively, these results extend the role of this pleiotropic growth factor to shaping sleep architecture through regulation of orexin neurons. We speculate that poor sleep quality associated to diverse conditions may be related to disturbed brain IGF-I input to orexin neurons.

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“…Hepatic nuclear receptor TFs are important modulators of liver circadian networks, as demonstrated by HNF4A ChIP‐seq in mouse livers, which showed that binding of this TF to chromatin is rhythmic (Qu et al, ). Liver metabolic pathways, such as insulin signaling, are also involved in circadian rhythm regulation (Crosby et al, ; E. E. Zhang et al, ), indicating that the relationship between clock and metabolism is bidirectional. This notion has been further corroborated by studies describing global changes of circadian transcriptional and epigenomic landscapes in diet‐induced obesity models (Eckel‐Mahan et al, ; Kohsaka et al, ).…”

Section: Liver Enhancer Dynamicsmentioning

confidence: 99%

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

Cebola

2020

WIREs Mechanisms of Disease

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Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) result from complex interactions between intrinsic and extrinsic factors, including genetics and exposure to obesogenic environments. These risk factors converge in aberrant gene expression patterns in the liver, which are underlined by altered cis‐regulatory networks. In homeostasis and in disease states, liver cis‐regulatory networks are established by coordinated action of liver‐enriched transcription factors (TFs), which define enhancer landscapes, activating broad gene programs with spatiotemporal resolution. Recent advances in DNA sequencing have dramatically expanded our ability to map active transcripts, enhancers and TF cistromes, and to define the 3D chromatin topology that contains these elements. Deployment of these technologies has allowed investigation of the molecular processes that regulate liver development and metabolic homeostasis. Moreover, genomic studies of NAFLD patients and NAFLD models have demonstrated that the liver undergoes pervasive regulatory rewiring in NAFLD, which is reflected by aberrant gene expression profiles. We have therefore achieved an unprecedented level of detail in the understanding of liver cis‐regulatory networks, particularly in physiological conditions. Future studies should aim to map active regulatory elements with added levels of resolution, addressing how the chromatin landscapes of different cell lineages contribute to and are altered in NAFLD and NAFLD‐associated metabolic states. Such efforts would provide additional clues into the molecular factors that trigger this disease. This article is categorized under: Biological Mechanisms > Metabolism Biological Mechanisms > Regulatory Biology Laboratory Methods and Technologies > Genetic/Genomic Methods

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Insulin/IGF-1 Drives PERIOD Synthesis to Entrain Circadian Rhythms with Feeding Time

Cited by 256 publications

References 91 publications

Ontogeny and function of the circadian clock in intestinal organoids

Ontogeny and function of the circadian clock in intestinal organoids

Insulin-Like Growth Factor I Modulates Sleep Through Hypothalamic Orexin Neurons

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

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