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Neuregulin 4 mediates the metabolic benefits of mild cold exposure by promoting beige fat thermogenesis

ABSTRACT: Neuregulin 4 mediates the metabolic benefits of mild cold exposure by promoting beige fat thermogenesis

PROVIDER: PRJNA1035510 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26666679.fastq.gz	Fastqsanger.gz
	SRR26666680.fastq.gz	Fastqsanger.gz
	SRR26666681.fastq.gz	Fastqsanger.gz
	SRR26666682.fastq.gz	Fastqsanger.gz
	SRR26666683.fastq.gz	Fastqsanger.gz

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Neuregulin 4 mediates the metabolic benefits of mild cold exposure by promoting beige fat thermogenesis

Project description:Interorgan crosstalk via secreted hormones and metabolites is a fundamental aspect of mammalian metabolic physiology. Beyond the highly specialized endocrine cells, peripheral tissues are emerging as an important source of metabolic hormones that influence energy and nutrient metabolism and contribute to disease pathogenesis. Neuregulin 4 (Nrg4) is a fat-derived hormone that protects mice from nonalcoholic steatohepatitis (NASH) and NASH-associated liver cancer by shaping hepatic lipid metabolism and the liver immune microenvironment. Despite its enriched expression in brown fat, whether NRG4 plays a role in thermogenic response and mediates the metabolic benefits of cold exposure remain unexplored. Here we show that Nrg4 expression in inguinal white adipose tissue (iWAT) is highly responsive to chronic cold exposure. Nrg4 deficiency impairs beige fat induction and renders mice more susceptible to diet-induced metabolic disorders under mild cold conditions. Using mice with adipocyte and hepatocyte-specific Nrg4 deletion, we reveal that adipose tissue-derived NRG4, but not hepatic NRG4, is essential for beige fat induction following cold acclimation. Furthermore, treatment with recombinant NRG4-Fc fusion protein promotes beige fat induction in iWAT and improves metabolic health in diet-induced obese mice. These findings highlight a critical role of NRG4 in mediating beige fat induction and preserving metabolic health under mild cold conditions.

2024-01-01 | GSE246993 | GEO

Neuregulin 4 mediates the metabolic benefits of mild cold exposure by promoting beige fat thermogenesis.

Project description: Not available

| S-EPMC10906454 | biostudies-literature

The Histone Methyltransferase SUV420H2 Regulates Brown and Beige Adipocyte Thermogenesis

Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.

2024-05-09 | GSE244457 | GEO

The Histone Methyltransferase SUV420H2 Regulates Brown and Beige Adipocyte Thermogenesis (ATAC-Seq)

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Naa10p Inhibits Beige Adipocyte-mediated Thermogenesis through N-alpha-acetylation of Pgc1-alpha

Project description:We report that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, beige adipocyte differentiation and activation. Mechanistically, Naa10p acetylates the N-terminus of Pgc1-alpha and prevents it from interacting with Ppar[gamma] to activate key genes, such as Ucp1, involved in beige adipocyte function.

2019-08-15 | GSE133726 | GEO

Naa10p Inhibits Beige Adipocyte-mediated Thermogenesis through N-α-acetylation of Pgc1α

Project description:We reported that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, beige adipocyte differentiation and activation. Mechanistically, Naa10p acetylates the N-terminus of Pgc1α and prevents it from interacting with Ppar to activate key genes, such as Ucp1, involved in beige adipocyte function. We used microarrays to profile the gene expression changes by Naa10p KO in inguinal white adipose tissues (iWATs) derived from mice fed with high fat diet for 15 weeks.

2019-08-16 | GSE133865 | GEO

The miR-182-5p/FGF21/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis

Project description:The miR-182-5p/FGF21/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis miR182 overexpression in primary cultured iWAT

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The Histone Methyltransferase SUV420H2 Regulates Brown and Beige Adipocyte Thermogenesis

Project description:The Histone Methyltransferase SUV420H2 Regulates Brown and Beige Adipocyte Thermogenesis

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RNA-sequencing of Control and TLE3-deficient Beige Adipocytes

Project description:Prolonged cold exposure stimulates the recruitment of beige adipocytes within white adipose tissue. Beige adipocytes depend on mitochondrial oxidative phosphorylation to drive thermogenesis. The transcriptional coregulator TLE3 inhibits mitochondrial and metabolic gene expression in beige adipocytes.

2019-05-23 | GSE116894 | GEO

Wnt/β-catenin signaling restrains developmental beige adipocyte thermogenesis and its inhibition imprints long-term energy expenditure_Inguinal white adipose tissue (iWAT) from 4-week-old male mice

Project description:Beige adipocytes that emerge during the peri-weaning period support sympathetic nervous system (SNS)-independent thermogenesis, yet the mechanisms governing this spontaneous beiging remain unclear.

2026-01-10 | GSE315581 | GEO

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