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Diurnal oscillations in murine brown adipose tissue analyzed by ChIP-seq

ABSTRACT: Diurnal oscillations in murine brown adipose tissue analyzed by ChIP-seq

PROVIDER: PRJNA809572 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18110661.fastq.gz	Fastqsanger.gz
	SRR18110662.fastq.gz	Fastqsanger.gz
	SRR18110663.fastq.gz	Fastqsanger.gz
	SRR18110664.fastq.gz	Fastqsanger.gz
	SRR18110665.fastq.gz	Fastqsanger.gz

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Diurnal oscillations in murine brown adipose tissue analyzed by RNA-seq

Project description:Diurnal oscillations in murine brown adipose tissue analyzed by RNA-seq

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Diurnal oscillations in murine brown adipose tissue analyzed by RNA-seq

Project description:Brown adipose tissue (BAT) burns fatty acids to produce heat, and shows diurnal oscillation with peak activity in glucose and triglyceride-derived fatty acid uptake at wakening. To gain further insight in the diurnal regulation of metabolic BAT activity, we performed RNA-sequencing (RNA-seq) on interscapular (i)BAT samples collected from chow-fed male C57BL/6J mice (10 weeks old) exposed to mild cold (22°C) at 3-hour intervals throughout a 24-hour period (n=4 mice per time point). All mice were entrained to a 12h:12h light:dark cycle, and therefore time is denoted as Zeitgeber Time (ZT) in which ZT0 indicates the onset of the light (active) phase.

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Project description:OBJECTIVE: Brown adipose tissue (BAT) burns fatty acids (FAs) to produce heat, and shows diurnal oscillation in glucose and triglyceride (TG)-derived FA-uptake, peaking around wakening. Here we aimed to gain insight in the diurnal regulation of metabolic BAT activity.METHODS: RNA-sequencing, chromatin immunoprecipitation (ChIP)-sequencing and lipidomics analyses were performed on BAT samples of wild type C57BL/6J mice collected at 3-h intervals throughout the day. Knockout and overexpression models were used to study causal relationships in diurnal lipid handling by BAT.RESULTS: We identified pronounced enrichment of oscillating genes involved in extracellular lipolysis in BAT, accompanied by oscillations of FA and monoacylglycerol content. This coincided with peak lipoprotein lipase (Lpl) expression, and was predicted to be driven by peroxisome proliferator-activated receptor gamma (PPARγ) activity. ChIP-sequencing for PPARγ confirmed oscillation in binding of PPARγ to Lpl. Of the known LPL-modulators, angiopoietin-like 4 (Angptl4) showed the largest diurnal amplitude opposite to Lpl, and both Angptl4 knockout and overexpression attenuated oscillations of LPL activity and TG-derived FA-uptake by BAT.CONCLUSIONS: Our findings highlight involvement of PPARγ and a crucial role of ANGPTL4 in mediating the diurnal oscillation of TG-derived FA-uptake by BAT, and imply that time of day is essential when targeting LPL activity in BAT to improve metabolic health.

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