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The polymethoxyflavone Sudachitin modulates the circadian clock to enhance energy metabolism and remodel liver physiology

ABSTRACT: The polymethoxyflavone Sudachitin modulates the circadian clock to enhance energy metabolism and remodel liver physiology

PROVIDER: PRJNA871200 | ENA |

REPOSITORIES: ENA

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The polymethoxyflavone Sudachitin modulates the circadian clock to enhance energy metabolism and remodel liver physiology

Project description:Polymethoxylated flavones (PMFs) are a group of natural compounds known to display a wide array of beneficial effects to promote physiological fitness. Recent studies revealed circadian clocks as an important cellular mechanism mediating the preventive efficacy of the major PMF Nobiletin against metabolic disorders. Sudachitin is a PMF enriched in Citrus sudachi, and its functions and mechanism of action are poorly understood. Using circadian reporter cells, we showed that Sudachitin modulated circadian amplitude and period of Bmal1 promoter-driven reporter rhythms, and real-time qPCR analysis showed that Sudachitin altered expression of core clock genes, notably Bmal1, at both transcript and protein levels. Mass-spec analysis revealed systemic exposure in vivo. In mice fed with high-fat diet with or without Sudachitin, we observed increased nighttime activity and daytime sleep, accompanied by significant metabolic improvements in a circadian time-dependent manner, including respiratory quotient, blood lipid and glucose profiles and liver physiology. Focusing on the liver, RNA-sequencing and metabolomic analyses revealed prevalent diurnal remodeling in both gene expression and metabolite accumulation. Taken together, our study elucidates Sudachitin as a new clock-modulating PMF with hepatic remodeling functions to improve systemic metabolic homeostasis, and highlights the circadian clock as a fundamental mechanism to safeguard physiological well-being.

2023-03-01 | GSE211612 | GEO

Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy

Project description:Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy

| PRJNA674502 | ENA

Liver Clock Rescue

Project description:Circadian clocks drive 24-h rhythms of physiology and behavior. The circadian clock of hepatocytes has been shown to regulate glucose metabolism, and we were interested if rescuing liver clock function can reverse metabolic impairments in hyperphagic/obese Clock-D19 mutant mice. We compared transcripomte regulation in livers (at Zeitgeber time ZT10) of wild-type (C57BL/6J) and Clock-D19 mice and Clock-D19 mice with genetic rescue of liver clock function using hydrodynamic tail vein injection of a WT-CLOCK expression plasmid

2017-03-31 | GSE94838 | GEO

Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy [SZ14]

Project description:Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy [SZ14]

| PRJNA674507 | ENA

Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy [SZ9]

Project description:Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy [SZ9]

| PRJNA674500 | ENA

transcriptional analysis of breast circadian clock

Project description:Circadian clocks drive ~24 hr rhythms in tissue physiology. They rely on transcriptional/translational feedback loops driven by interacting networks of clock complexes.To gain insights into the role of the mammary clock, circadian time-series microarrays were performed to identify rhythmic genes in vivo. Breast tissues were isolated at 4 hr intervals for two circadian (24 hourly) cycles, from mice kept under constant darkness to avoid any light- or dark-driven genes.

2017-12-01 | E-MTAB-5330 | biostudies-arrayexpress

Leveraging CD16 fusion receptors to remodel the immune response for enhancing iPSC-derived NK cell anti-tumor immunotherapy

Project description:We developed a novel hnCD16FR construct that exhibit more potent cytotoxicity than reported hnCD16, which is a promising approach to treating hematologic malignancies and solid tumors with improved ADCC properties. We also offer a rationale for NK activation domains that remodel immune response to enhance CD16 signaling in NK cells.

2023-06-21 | GSE223656 | GEO

The circadian clock coordinates ribosome biogenesis.

Project description:Evolutionary conserved biological rhythms play a fundamental role in the physiology and behavior of all light-sensitive organisms. Generation of rhythmic expression of clock-controlled genes is orchestrated by a molecular circadian clock constitutes by interconnected negative feedback loops of transcription factors. In this study, we want to characterize gene which also present a rhythmic translation through the characterization of genes with a rhythmic polysomal/total RNA ratio.

2012-12-01 | GSE33726 | GEO

Control of rhythmic translation by the circadian clock

2012-12-01 | E-GEOD-33726 | biostudies-arrayexpress

Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in the phase entrainment of rhythmic behavior and physiology

Project description:The circadian clock represents an evolutionarily acquired gene network that synchronizes physiology to anticipate environmental changes caused by the succession of day and night. While most mammalian cells have a circadian clock, their synchronization depends on a central pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus that integrates light signals. While peripheral organs can be also synchronized by feeding cues and can be uncoupled from the central pacemaker, no impact of peripheral organs on the central clock has been yet observed. Here, we used a mouse chimeric model in which mouse hepatocytes have been replaced by human hepatocytes that have different circadian and signaling properties to characterize such potential feedback. Remarkably, we observed that liver humanization rewired the liver diurnal gene expression and advance the circadian clock by approximately 4 hours. Strikingly, this phase advance was also observed in the muscle and for the entire rhythmic physiology of the animals, with an impact of human hepatocytes on the circadian function of the central clock. Like mice with a deficient central clock, the humanized animals shifted their physiology more rapidly to the light phase under day feeding. This data prompt to reconsider the role of peripheral clocks on the central pacemaker and offers new perspective to understand the impact of diseased organs on the global circadian physiology.

2023-05-25 | GSE212079 | GEO

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