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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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			Action	DRS
	SRR21136974_1.fastq.gz	Fastqsanger.gz
	SRR21136974_2.fastq.gz	Fastqsanger.gz
	SRR21136975_1.fastq.gz	Fastqsanger.gz
	SRR21136975_2.fastq.gz	Fastqsanger.gz
	SRR21136976_1.fastq.gz	Fastqsanger.gz

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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.

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

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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.

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