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DICER is downregulated in mouse adipose tissue during high-fat diet feeding

ABSTRACT: DICER is downregulated in mouse adipose tissue during high-fat diet feeding

PROVIDER: PRJNA1070687 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27766134.fastq.gz	Fastqsanger.gz
	SRR27766135.fastq.gz	Fastqsanger.gz
	SRR27766136.fastq.gz	Fastqsanger.gz
	SRR27766137.fastq.gz	Fastqsanger.gz
	SRR27766138.fastq.gz	Fastqsanger.gz

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DICER is downregulated in mouse adipose tissue during high-fat diet feeding

Project description:The adipose tissue plays an important role in controlling whole-body energy balance, and proper regulation of adipose tissue function is essential for metabolic health. In response to energy surplus, the adipose tissue needs to expand, which may lead to local areas of hypoxia within the tissue. This is thought to promote whole-body insulin resistance. Here we report that DICER, a key enzyme in the maturation of miRNAs and a potential marker of adipocyte health, is profoundly downregulated in mouse adipose tissue within the first week of high-fat diet (HFD) feeding, and this effect is sustained in response to long-term HFD feeding. The downregulation of DICER protein occurs in both mature adipocytes and in the stromal vascular cells. Mechanistically, we provide evidence that hypoxia and hypoxia-inducible factor 1-α (HIF1α) facilitate ubiquitination of DICER to target it for autophagy-mediated degradation, and we show that DICER and HIF1α interact in adipose tissue after HFD feeding, which may signal for DICER degradation. Finally, despite reductions in DICER protein, we were not able to detect any differences in global miRNA levels in subcutaneous adipose tissue of mice after one or three weeks of HFD-feeding. In conclusion, the nutritional challenge of HFD feeding in mice leads to a large reduction in adipose tissue DICER protein, which is induced by hypoxia during tissue expansion and mediated through an interaction with HIF1α.

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Project description:The effect of high fat diet feeding on adipose tissue gene transcription regulation was investigated in C57Bl/6J mice using Affymetrix gene expression arrays. Expression profiling was determined in 5 months old male mice showing heterogeneous metabolic, hormonal and behavioral adaptation to high fat diet (40% fat) feeding for 15 weeks. Control mice were fed a standard carbohydrate chow. Six animals per group were used.

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Mouse adipose tissue under hypercaloric and isocaloric high-fat diet

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