Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetic and pharmacological targeting of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis

ABSTRACT: Genetic and pharmacological targeting of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis

PROVIDER: PRJNA1105091 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR28816245.fastq.gz	Fastqsanger.gz
	SRR28816246.fastq.gz	Fastqsanger.gz
	SRR28816247.fastq.gz	Fastqsanger.gz
	SRR28816248.fastq.gz	Fastqsanger.gz
	SRR28816249.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Genetic and pharmacological targeting of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis

Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. We report that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator activated receptor-alpha (PPARα) transcription and fatty acid β-oxidation (FAO), and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In male mice with diet-induced MASH, blocking oxalate overproduction through hepatocyte-specific AGXT overexpression or pharmacological inhibition of LDHA potently lower steatosis, inflammation, and fibrosis by inducing PPARα-driven FAO, and suppressing monocyte chemotaxis, nuclear factor-kappaB and transforming growth factor-beta targets. These findings highlight hepatic oxalate overproduction as a new target for the treatment of MASH.

2024-08-07 | GSE265985 | GEO

Raw data for : "Genetic and pharmacological targeting of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis"

Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. We report that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator activated receptor-alpha (PPARa) transcription and fatty acid b-oxidation (FAO), and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In male mice with diet-induced MASH, blocking oxalate overproduction through hepatocyte-specific AGXT overexpression or pharmacological inhibition of LDHA potently lower steatosis, inflammation, and fibrosis by inducing PPARa-driven FAO, and suppressing monocyte chemotaxis, nuclear factor-kappa B and transforming growth factor-beta targets. These findings highlight hepatic oxalate overproduction as a new target for the treatment of MASH.

2024-04-21 | MSV000094587 | MassIVE

Modulation of Microbial Bile Acid Metabolism by DT-109 Ameliorates Nonalcoholic Steatohepatitis in Nonhuman Primates

Project description:Modulation of Microbial Bile Acid Metabolism by DT-109 Ameliorates Nonalcoholic Steatohepatitis in Nonhuman Primates

2023-02-10 | PXD040009 |

FABP4 deficiency ameliorates alcoholic steatohepatitis in mice

Project description:FABP4 deficiency ameliorates alcoholic steatohepatitis in mice

| PRJNA1104153 | ENA

SOX9 ameliorates nonalcoholic steatohepatitis through activating AMPK pathway

Project description:SOX9 ameliorates nonalcoholic steatohepatitis through activating AMPK pathway

| PRJNA993674 | ENA

Liver lipophagy ameliorates nonalcoholic steatohepatitis through lysosomal lipid exocytosis

Project description:Liver lipophagy ameliorates nonalcoholic steatohepatitis through lysosomal lipid exocytosis

| PRJNA771352 | ENA

Pharmacological inhibition of G9a ameliorates pulmonary vascular remodeling in PAH

Project description:Pharmacological inhibition of G9a ameliorates pulmonary vascular remodeling in PAH

| PRJNA826869 | ENA

Biotransformed Bear Bile Powder Ameliorates Diet-induced Nonalcoholic Steatohepatitis in Mice

Project description:Biotransformed Bear Bile Powder Ameliorates Diet-induced Nonalcoholic Steatohepatitis in Mice

| PRJNA1014000 | ENA

FABP4 deficiency ameliorates alcoholic steatohepatitis in mice

Project description:Fatty acid-binding protein 4 (FABP4) plays an essential role in metabolism and inflammatory. However, the role of FABP4 in alcoholic steatohepatitis (ASH) remains unclear. This study aimed to investigate the function of FABP4 and the underlying mechanisms in the progression of ASH.

2024-04-24 | GSE265758 | GEO

Liver lipophagy ameliorates nonalcoholic steatohepatitis through lysosomal lipid exocytosis

Project description:Nonalcoholic steatohepatitis (NASH) is a progressive disorder with aberrant lipid accumulation and subsequent inflammatory and profibrotic response. Lipid reduction through cytoplasmic lipolysis might adversely worsen steatohepatitis, however, the effect of autophagic lipolysis, lipophagy, remains obscure. We engineered the adaptor protein to induce lipophagy with lipid droplet targeting signal and modified LC3 interacting region. Activating hepatocyte lipophagy obviously mitigated both steatosis and NASH pathology. Mechanistically, lipophagy promoted the excretion of lipid from liver via lysosomal exocytosis and attenuated harmful accumulation of nonesterified fatty acid. This exocytosis was dependent on Ca2+ signal unlike the lysosomal dysfunction-related exocytosis. High content compound screening identified alpelisib and digoxin, clinically-approved compounds, as effective activators of lipophagy. Administration of alpelisib or digoxin inhibited the transition to steatohepatitis in mice fed high fat with low methionine low choline diet. Given all these data, activating lipophagy may be a promising therapeutic approach to prevent NASH progression.

2023-05-15 | GSE185911 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data