Evidence for ~12-h ultradian gene programs in humans

Deleted Journal, Journal Year: 2024, Volume and Issue: 1(1)

Published: Aug. 9, 2024

Mice and many marine organisms exhibit ~12-h ultradian rhythms, however, direct evidence of rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling peripheral white blood cells from three healthy humans. All participants independently exhibited robust transcriptional molecular programs involved RNA protein metabolism, with strong homology to circatidal gene previously identified Cnidarian species.

Language: Английский

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Preservation of ∼12-h ultradian rhythms of gene expression of mRNA and protein metabolism in the absence of canonical circadian clock

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: May 30, 2023

Introduction: Besides the ∼24-h circadian rhythms, ∼12-h ultradian rhythms of gene expression, metabolism and behaviors exist in animals ranging from crustaceans to mammals. Three major hypotheses were proposed on origin mechanisms regulation namely, that they are not cell-autonomous controlled by a combination clock environmental cues, regulated two anti-phase transcription factors cell autonomous manner, or established oscillator. Methods: To distinguish among these possibilities, we performed post hoc analysis high temporal resolution transcriptome dataset cells lacking canonical clock. Results: In both liver BMAL1 knockout mice Drosophila S2 cells, observed robust prevalent expression enriched fundamental processes mRNA protein show large convergence with those identified wild-type liver. Bioinformatics further predicted ELF1 ATF6B as putative regulating independently fly mice. Discussion: These findings provide additional evidence support existence an evolutionarily conserved 12-h oscillator controls multiple species.

Language: Английский

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Data integration and analysis for circadian medicine

Acta Physiologica, Journal Year: 2023, Volume and Issue: 237(4)

Published: Feb. 15, 2023

Abstract Data integration, data sharing, and standardized analyses are important enablers for data‐driven medical research. Circadian medicine is an emerging field with a particularly high need coordinated systematic collaboration between researchers from different disciplines. Datasets in circadian multimodal, ranging molecular profiles clinical parameters to physiological measurements obtained (wearable) sensors or reported by patients. Uniquely, spanning both the time dimension spatial (across tissues) needed obtain holistic view of system. The study human rhythms context has confront heterogeneity clock properties within across subjects our inability repeatedly relevant biosamples one subject. This requires informatics solutions integrating visualizing types at various temporal resolutions milliseconds seconds minutes several hours. Associated challenges range lack standards that can be used represent all required common interoperable form, related storage, perform transformations integrated visualizations, privacy issues. downstream analysis specialized approaches identification, characterization, discrimination rhythms. We conclude research provides ideal environment developing innovative methods address collection, visualization, multimodal multidimensional biomedical data.

Language: Английский

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Single and Multiple Doses of Seladelpar Decrease Diurnal Markers of Bile Acid Synthesis in Mice

PPAR Research, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Peroxisome proliferator-activated receptors (PPARs) modulate bile metabolism and are important therapeutic options in cholestatic diseases. This study was aimed at understanding the effects of single multiple doses seladelpar, a PPARδ (peroxisome receptor delta) agonist, on plasma C4 (a freely diffusible metabolite accepted as proxy for de novo acid biosynthesis), Fibroblast Growth Factor 21 (Fgf21), gene expression changes liver male female mice. C57BL/6 mice were treated with seladelpar 10 mg/kg/day or vehicle through oral gavage before lights out Day 1 (single dose) from to 7 (multiple doses). Liver samples obtained 0, 1, 2, 4, 8, 12, 16, 24 h postdosing, Fgf21 levels measured. In vehicle-treated mice, higher dark cycle compared light cycle, females than males. Plasma did not vary substantially over dark-light show sex-specific pattern. Seladelpar treatment significantly reduced increased both sexes, which coincided decrease cholesterol 7α-hydroxylase mRNA an increase livers. Untargeted RNA sequencing revealed strong correlation between genes differentially expressed after single- multiple-dose treatment. PPAR-responsive genes, including pyruvate dehydrogenase kinase acyl-CoA thioesterase angiopoietin-like upregulated. No nuclear receptors, clock observed. Overall, these results consistent model where reduces synthesis by upregulating modulating other genes.

Language: Английский

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Interferência dos ritmos ultradianos no metabolismo e sua relação com doenças endócrinas

STUDIES IN HEALTH SCIENCES, Journal Year: 2025, Volume and Issue: 6(1), P. e14781 - e14781

Published: March 14, 2025

Os ritmos ultradianos são ciclos biológicos menores que 24 horas regulam a secreção pulsátil de hormônios essenciais para homeostase metabólica, incluindo insulina, cortisol e hormônio do crescimento. Esses influenciam diretamente o metabolismo energético, resposta inflamatória regulação da glicose. Sua desregulação tem sido associada doenças endócrinas, como diabetes tipo 2, obesidade distúrbios tireoidianos. Este estudo realizou uma revisão integrativa literatura analisar relação entre metabolismo, avaliando sua influência na hormonal no desenvolvimento metabólicas. A incluiu pesquisas extraídas bases dados científicas PubMed, LILACS, Scopus, Web of Science Embase, considerando artigos publicados nos últimos 10 anos. análise dos estudos revelou perda regularidade compromete funcionalidade osciladores hormonais centrais periféricos, resultando em metabólicos severos. Além disso, fatores padrões alimentares irregulares privação sono contribuem desses hormonais. achados desta destacam importância cronobiologia prevenção tratamento endócrinas. Estratégias terapêuticas baseadas modulação ultradianos, cronoterapia ajuste alimentação ciclo sono, mostraram-se eficazes restauração equilíbrio metabólico. No entanto, mais necessários desenvolver abordagens personalizadas otimizem sincronização promovam melhor qualidade vida indivíduos com endócrinos.

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Circadian clock controlled glycolipid metabolism and its relevance to disease management

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116967 - 116967

Published: April 1, 2025

Language: Английский

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Nuclear speckle rejuvenation alleviates proteinopathies at the expense of YAP1

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 21, 2024

Abstract Current treatments targeting individual protein quality control have limited efficacy in alleviating proteinopathies, highlighting the prerequisite for a common upstream druggable target capable of global proteostasis modulation. Building on our prior research establishing nuclear speckles as pivotal membrane-less organelle responsible transcriptional control, we aim to alleviate proteinopathies through speckle rejuvenation. We identified pyrvinium pamoate small-molecule rejuvenator that enhances while suppressing YAP1 signaling via decreasing surface/interfacial tension condensates interaction with intrinsically disordered region scaffold SON. In pre-clinical models, nanomolar alleviated retina degeneration and reduced tauopathy by promoting autophagy ubiquitin-proteasome system SON-dependent manner without causing cellular stress. Aberrant morphology, increased activity were also observed human tauopathies. Our study uncovers novel therapeutic targets tackling misfolding disorders within an expanded framework encompassing YAP1.

Language: Английский

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Circadian rhythms and the liver

Liver International, Journal Year: 2022, Volume and Issue: 43(3), P. 534 - 545

Published: Dec. 29, 2022

Abstract This narrative review briefly describes the mammalian circadian timing system, specific features of liver clock, also by comparison with other peripheral clocks, role clock in preparation food intake, and its relationship energy metabolism. It then goes on to provide a chronobiological perspective pathophysiology management several types disease, particular focus metabolic‐associated fatty disease (MAFLD), decompensated cirrhosis transplantation. Finally, it provides some insight into potential contribution principles hygiene practices preventing MAFLD, improving prognosis advanced modulating transplantation outcomes.

Language: Английский

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Evidence for conservation of primordial ∼12-hour ultradian gene programs in humans under free-living conditions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 2, 2023

Abstract While circadian rhythms are entrained to the once daily light-dark cycle of sun, many marine organisms exhibit ∼12h ultradian corresponding twice movement tides. Although human ancestors emerged from circatidal environment millions years ago, direct evidence in humans is lacking. Here, we performed prospective, temporal transcriptome profiling peripheral white blood cells and identified robust transcriptional three healthy participants. Pathway analysis implicated RNA protein metabolism, with strong homology gene programs previously Cnidarian species. We further observed intron retention events genes involved MHC class I antigen presentation, synchronized expression mRNA splicing all Gene regulatory network inference revealed XBP1, GABP KLF transcription factor family members as potential regulators rhythms. These results suggest that biological have a primordial evolutionary origin important implications for health disease.

Language: Английский

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Reduced glucose concentration enhances ultradian rhythms in Pdcd5 promoter activity in vitro

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 11, 2023

Intrinsically driven ultradian rhythms in the hourly range are often co-expressed with circadian various physiological processes including metabolic such as feeding behaviour, gene expression and cellular metabolism. Several behavioural observations show that reduced energy intake or increased expenditure leads to a re-balancing of timing, favouring activity patterns when availability is limited. This suggests close link between rhythmicity homeostasis, but we currently lack models test this hypothesis at level. We therefore transduced 3T3-L1 pre-adipocyte cells reporter construct drives destabilised luciferase via Pdcd5 promotor, previously showed exhibit robust vitro . Ultradian promotor bioluminescence was observed >80% all cultures were synchronised dexamethasone, whereas significantly lower numbers exhibited non-synchronised (∼11%). Cosine fits cultured measured low glucose concentrations (2 mM 5 mM), higher amplitudes than other cultures, shorter period (6.9 h vs. 8.2 h, N = 12). Our findings substantial which clocks have been , line synchronisation rhythms. Critically, amplitude enhanced conditions, suggesting enhances level

Language: Английский

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