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Transcriptional effects of KLF15 deletion in brown adipose tissue in response to fasting and cold

ABSTRACT: Transcriptional effects of KLF15 deletion in brown adipose tissue in response to fasting and cold

PROVIDER: PRJNA740193 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14887067_1.fastq.gz	Fastqsanger.gz
	SRR14887067_2.fastq.gz	Fastqsanger.gz
	SRR14887068_1.fastq.gz	Fastqsanger.gz
	SRR14887068_2.fastq.gz	Fastqsanger.gz
	SRR14887069_1.fastq.gz	Fastqsanger.gz

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Transcriptional effects of KLF15 deletion in brown adipose tissue in response to fasting and cold

Project description:We report bulk RNA-sequencing of brown adipose tissue (BAT) harvested from K15flox/flox and BAT specific KLF15 knockout (K15-BKO) mice in response to cold challenge and fasting

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p53 regulates a miRNA-fructose transporter axis in brown adipose tissue under fasting

Project description:Active thermogenic adipocytes voraciously consume energy substrates like fatty acids and glucose to maintain body temperature upon cold exposure. Despite strong evidence for the involvement of brown adipose tissue (BAT) in controlling systemic energy homeostasis upon nutrient excess, it is unclear how the activity of brown adipocytes is regulated in times of nutrient scarcity. Therefore, this study aimed to scrutinize factors that modulate BAT activity to balance thermogenic and energetic needs upon simultaneous fasting and cold-exposure. For an unbiased view we performed transcriptomic and miRNA sequencing analysis of BAT from acutely fasted (24 hours) mice under mild cold exposure. Combining these data with in-depth bioinformatic analyses and in vitro experiments, we defined a previously undescribed axis of p53 and miR-92a-1-5p that is highly upregulated by fasting in thermogenic adipocytes. p53, a fasting-responsive transcription factor, was previously shown to control genes involved in the thermogenic program and miR-92a-1-5p was found to negatively correlate with human BAT activity. Here, we elucidated fructose transporter Slc2a5 as one direct downstream target of this axis and show that fructose can be taken up by and metabolized in brown adipocytes. In sum, this study delineates a fasting-induced pathway involving p53 and miR-92a-1-5p impinging on Slc2a5 and suggests a contribution of fructose as an energy substrate in thermogenic adipocytes.

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Project description:We applied RNA sequencing (RNA-seq) to map the global changes in gene expression of interscapular brown adipose tissue (iBAT) of mice subjected to acute cold exposure for 3 days. Here we find extensive changes in the iBAT transcriptome in response to cold with a prominent induction of genes associated to lipid-related metabolic processes. RNA-seq of poly-A enriched RNA isolated from brown adipose tissue of 5 mice housed at room temperature (22Â°C) and 5 mice exposed to cold (4Â°C) for 3 days.

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