The hepatocyte insulin receptor is required to program the liver clock and rhythmic gene expression DOI Creative Commons

Tiffany Fougeray,

Arnaud Polizzi, Marion Régnier

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 39(2), P. 110674 - 110674

Published: April 1, 2022

Liver physiology is circadian and sensitive to feeding insulin. Food intake regulates insulin secretion a dominant signal for the liver clock. However, how much contributes effect of on clock rhythmic gene expression remains be investigated. Insulin action partly depends changes in receptor (IR)-dependent expression. Here, we use hepatocyte-restricted deletion IR evaluate its role regulation oscillation as well programming adult mouse liver. We find that, absence IR, rhythmicity core-clock altered response day-restricted feeding. This change associated with defective reprogramming Our data show that an intact hepatocyte required program

Language: Английский

Sex-dimorphic and age-dependent organization of 24-hour gene expression rhythms in humans DOI
Lorenzo Figà Talamanca, Cédric Gobet, Félix Naef

et al.

Science, Journal Year: 2023, Volume and Issue: 379(6631), P. 478 - 483

Published: Feb. 2, 2023

The circadian clock modulates human physiology. However, the organization of tissue-specific gene expression rhythms and how these depend on age sex is not defined in humans. We combined data from Genotype-Tissue Expression (GTEx) project with an algorithm that assigns phases to 914 donors, by integrating temporal information multiple tissues each individual, identify messenger RNA (mRNA) 46 tissues. Clock transcripts showed conserved timing relationships tight synchrony across body. mRNA varied breadth, covering global functions, including metabolic pathways systemic responses. structure was sexes groups. overall were highly sex-dimorphic more sustained females. Rhythmic programs generally dampened

Language: Английский

Citations

100
Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals DOI Creative Commons
Shaunak Deota, Terry Lin, Amandine Chaix

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(1), P. 150 - 165.e4

Published: Jan. 1, 2023

Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of and fasting. In both animals humans, TRF has pleiotropic health benefits arise from multiple organ systems, yet the molecular basis TRF-mediated not well understood. Here, we subjected mice to isocaloric ad libitum (ALF) or western diet examined gene expression changes in samples taken 22 organs brain regions collected every 2 h over 24-h period. We discovered profoundly impacts expression. Nearly 80% all genes show differential rhythmicity under at least one tissue. Functional annotation these revealed tissue- pathway-specific TRF. These findings resources provide critical foundation for future mechanistic studies will help guide human time-restricted eating (TRE) interventions treat various disease conditions with without pharmacotherapies.

Language: Английский

Citations

68
Spatiotemporal Metabolic Liver Zonation and Consequences on Pathophysiology DOI Creative Commons
Tomaž Martini, Félix Naef, Jan S. Tchorz

et al.

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2023, Volume and Issue: 18(1), P. 439 - 466

Published: Jan. 24, 2023

Hepatocytes are the main workers in hepatic factory, managing metabolism of nutrients and xenobiotics, production recycling proteins, glucose lipid homeostasis. Division labor between hepatocytes is critical to coordinate complex complementary or opposing multistep processes, similar distributed tasks at an assembly line. This so-called metabolic zonation has both spatial temporal components. Spatial distribution function different lobular zones necessary perform sequential processes assign right environment. Moreover, control align required feeding fasting cycles. Disruption this spatiotemporal organization impairs key with local systemic consequences. Many diseases, such as nonalcoholic steatohepatitis diabetes, associated impaired liver zonation. Recent technological advances shed new light on gene expression networks controlling how their deregulation may be involved a large variety diseases. We summarize current knowledge about consequences pathobiology.

Language: Английский

Citations

51
Interorgan rhythmicity as a feature of healthful metabolism DOI
Joseph Bass

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(4), P. 655 - 669

Published: Feb. 8, 2024

Language: Английский

Citations

20
Brain-muscle communication prevents muscle aging by maintaining daily physiology DOI
Arun Kumar, Mireia Vaca-Dempere, Thomas Mortimer

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6695), P. 563 - 572

Published: May 2, 2024

A molecular clock network is crucial for daily physiology and maintaining organismal health. We examined the interactions importance of intratissue networks in muscle tissue maintenance. In arrhythmic mice showing premature aging, we created a basic module involving central peripheral (muscle) clock. Reconstituting brain-muscle sufficient to preserve fundamental homeostatic functions prevent aging. However, achieving whole requires contributions from other clocks. Mechanistically, acts as gatekeeper, selectively suppressing detrimental signals while integrating important functions. Our research reveals interplay between clocks function underscores impact eating patterns on these interactions.

Language: Английский

Citations

20
Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms DOI Creative Commons
Carolina M. Greco, Kevin B. Koronowski, Jacob G. Smith

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(39)

Published: Sept. 22, 2021

The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of lack specialized animal models, it unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we isolated interaction between feeding liver clock by reconstituting Bmal1 exclusively hepatocytes (Liver-RE), otherwise clock-less mice, controlling timing food intake. We found that cooperative action BMAL1 transcription factor CEBPB regulates transcriptional programs. Functionally, rhythm are sufficient temporal carbohydrate By contrast, rhythms tied redox lipid metabolism required communication skeletal muscle demonstrating cross-talk. Our results highlight inner workings system rely on communicating maintain metabolism.

Language: Английский

Citations

96
Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease DOI Creative Commons
Céline Jouffe, Benjamin D. Weger,

Eva Martín

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(10)

Published: March 1, 2022

Significance While increasing evidence associates the disruption of circadian rhythms with pathologic conditions, including obesity, type 2 diabetes, and nonalcoholic fatty liver diseases (NAFLD), involved mechanisms are still poorly described. Here, we show that, in both humans mice, pathogenesis NAFLD is associated clock combined perturbations growth hormone sex pathways. However, while this condition protects mice from development fibrosis insulin resistance, it correlates increased humans. This suggests that perturbation its pathways critical for metabolic diseases.

Language: Английский

Citations

69
Intercellular coupling between peripheral circadian oscillators by TGF-β signaling DOI Creative Commons
Anna‐Marie Finger,

Sebastian Jäschke,

Marta del Olmo

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(30)

Published: July 23, 2021

Paracrine TGF-β signaling is crucial to maintain robust and coherent circadian rhythms of peripheral oscillator networks.

Language: Английский

Citations

63
Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome DOI Creative Commons
Ana Carolina Dantas Machado, Steven D. Brown,

Amulya Lingaraju

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 40(1), P. 111008 - 111008

Published: July 1, 2022

Compositional oscillations of the gut microbiome are essential for normal peripheral circadian rhythms, both which disrupted in diet-induced obesity (DIO). Although time-restricted feeding (TRF) maintains synchrony and protects against DIO, its impact on dynamics cecal is modest. Thus, other regions gut, particularly ileum, nexus incretin bile acid signaling, may play an important role entraining rhythms. We demonstrate effect diet rhythms ileal composition transcriptome mice. The dynamic dampened DIO. TRF partially restores diurnal transcriptome, increases GLP-1 release, alters pool farnesoid X receptor (FXR) could explain how exerts metabolic benefits. Finally, we provide a web resource exploration data.

Language: Английский

Citations

62
Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice DOI Creative Commons
Jiyeon Lee, Julie Dimitry, Jong Hee Song

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 25, 2023

Alzheimer's disease, the most common age-related neurodegenerative is characterized by tau aggregation and associated with disrupted circadian rhythms dampened clock gene expression. REV-ERBα a core protein which also serves as nuclear receptor transcriptional repressor involved in lipid metabolism macrophage function. Global deletion has been shown to promote microglial activation mitigate amyloid plaque formation. However, cell-autonomous effects of healthy brain tauopathy are unexplored. Here, we show that enhances inflammatory signaling, disrupts metabolism, causes droplet (LD) accumulation specifically male microglia. These events impair phagocytosis, can be partially rescued blockage LD In vivo, exacerbates neuroinflammation two mouse models, mice. data demonstrate importance droplets reveal therapeutically accessible, sex-dependent regulator tauopathy.

Language: Английский

Citations

35