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ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits

ABSTRACT: ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits

PROVIDER: PRJNA993676 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23783200.fastq.gz	Fastqsanger.gz
	SRR23783201.fastq.gz	Fastqsanger.gz
	SRR23783202.fastq.gz	Fastqsanger.gz
	SRR23783203.fastq.gz	Fastqsanger.gz
	SRR23783204.fastq.gz	Fastqsanger.gz

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ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits

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ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits

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HGFAC is a ChREBP Regulated Hepatokine that Enhances Glucose and Lipid Homeostasis [RNA-Seq]

Project description:Carbohydrate Responsive Element-Binding Protein (ChREBP) is a carbohydrate sensing transcription factor that regulates both adaptive and maladaptive genomic responses in coordination of systemic fuel homeostasis. Genetic variants in the ChREBP locus associate with diverse metabolic traits in humans, including circulating lipids. To identify novel ChREBP-regulated hepatokines that contribute to its systemic metabolic effects, we integrated ChREBP ChIP-seq analysis in mouse liver with human genetic and genomic data for lipid traits and identified Hepatocyte Growth Factor Activator (HGFAC) as a promising ChREBP-regulated candidate in mice and humans. HGFAC is a protease that activates the pleiotropic hormone Hepatocyte Growth Factor (HGF). We demonstrate that HGFAC KO mice have phenotypes concordant with putative loss-of-function variants in human HGFAC. Moreover, in gain- and loss-of-function genetic mouse models, we demonstrate that HGFAC enhances lipid and glucose homeostasis, which may be mediated in part through actions to activate hepatic PPARγ activity. Together, our studies show that ChREBP mediates an adaptive response to overnutrition via activation of HGFAC in the liver to preserve glucose and lipid homeostasis.

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HGFAC is a ChREBP Regulated Hepatokine that Enhances Glucose and Lipid Homeostasis [ChIP-Seq]

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Proline hydroxylation of ChREBP

Project description:This project investigated proline hydroxylation of ChREBP. Proline hydroxylation was investigated in flag-IP enriched protein extracts from ChREBP-flag overexpressing HEK293 cells (A) and in ChREBP-IP enriched mouse liver protein (male, C57BL6/J) (B).

2020-10-19 | PXD019137 | Pride

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