Dataset Information

Study on the Mechanism of Action of Hippuric Acid Targeting the UGDH/FOXK1/CD36 Signaling Axis in Regulating Metabolic Dysfunction-AssociatedSteatotic Liver Diseases

ABSTRACT: Metabolic dysfunction-associated steatotic liver diseases (MASLD) is the most prevalent chronic liver disease globally, and the systemic metabolic disorders it triggers have become a serious public health concern. The endogenous metabolite hippuric acid (HA) is closely associated with a variety of metabolic disorders, but its molecular mechanisms in the progression of MASLD are not yet clear. Preliminary studies of this project have found that serum HA levels are significantly reduced in obese individuals and animals, and exogenous HA supplementation can alleviate body weight and liver fat accumulation in obese mice. It was also discovered that HA can reduce intracellular lipid deposition in hepatocytes by inhibiting CD36 expression. Mechanistic studies have revealed that HA can target UGDH, enhancing its binding with the transcription factor FOXK1, and inhibiting FOXK1 expression significantly reduces the transcription level of CD36. Therefore, the scientific hypothesis is proposed: HA inhibits liver fat accumulation by regulating the UGDH/FOXK1/CD36 signaling axis. This project will combine clinical sample analysis with in vitro and in vivo experiments to systematically elucidate the molecular mechanisms by which HA targets UGDH to inhibit nuclear expression of FOXK1, thereby regulating CD36 transcription. This will enhance our understanding of HA's role in lipid metabolism regulation and the development of MASLD and lay a theoretical foundation for uncovering effective therapeutic targets for MASLD.

ORGANISM(S): Mus musculus

PROVIDER: GSE299406 | GEO | 2026/03/11

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background & Aims Obesity is a major risk factor for metabolic associated steatotic liver disease (MASLD) which can progress from metabolic associated steatotic liver (MASL) to metabolic associated steatohepatitis (MASH). There are currently no effective and validated screening tools to stratify obese patients with a greater risk for MASH, independent of liver fibrosis, at a population level. We aimed to characterise the highly abundant and small protein plasma proteomes of worsening MASLD and overlay the liver-secreted proteome to generate a predictive model to stratify patients with and without MASH. Methods Venous blood and liver wedge biopsies were taken from 160 patients undergoing bariatric surgery. MASLD severity was assessed histologically. Liver biopsies from a subset of 96 patients were precision-cut and cultured to assess liver-secreted proteins. Proteomic analysis was performed using liquid chromatography-tandem mass spectrometry on the plasma and the incubation medium cutoff the liver slices. Results Current non-invasive scores failed to stratify MASH in our cohort. The top200 plasma proteome exhibited mild changes in patients with MASH compared to those with No pathology, while the SPEA approach identified substantial differences in plasma proteins of patients with MASH compared to those without MASH. Liver-secreted proteins were remodelled in MASH compared to MASL and individuals with No pathology. There were no significant changes in the liver-secreted proteins and plasma proteome when comparing MASL to those with No pathology. The APASHA model, comprised of APOF, PCSK9, AFM, and S100A6, HbA1c % and AZGP1 stratified MASH in the discovery (AUROC: 0.887, p<0.0001) and validation cohorts (AUROC:0.7673, p=0.0002) and outcompeted other non-invasive scores. Conclusions These proteomic investigations provide a detailed description of liver-secreted and plasma proteome with worsening MASLD. MASH remodels plasma and liver-secreted proteins. Plasma proteomics generated the APASHA model validated in two Australian bariatric cohorts. Further investigation is warranted to interrogate the utility of the APASHA model as a non-invasive risk prediction model in additional cohorts. Lay Summary: Metabolic-associated steatohepatitis (MASH), a more advanced form of metabolic-associated steatotic liver disease (MASLD), alters the levels of many proteins secreted by the liver and in the blood and those. The APASHA model, which is based on proteins that change in the blood or are secreted by the liver in cases of MASH, could potentially be developed into a simple blood test to predict MASH in high-risk groups.

Dataset Information

Study on the Mechanism of Action of Hippuric Acid Targeting the UGDH/FOXK1/CD36 Signaling Axis in Regulating Metabolic Dysfunction-AssociatedSteatotic Liver Diseases

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets