Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tripartite motif 46 aggravates MASLD progression by suppressing SGPL1- mediated hepatic lipophagy

ABSTRACT: Protein post-translational modifications (PTMs) participate in important bioactive regulatory processes and therefore can help elucidate the pathogenesis of Metabolic dysfunction-associated steatotic liver disease (MASLD). Ubiquitination modification plays a vital role in regulating the inflammatory response and fibrosis in MASLD process. Here, we performed multi-omics analysis to demonstated that TRIM46 binds directedly with SGPL1, promoting SGPL1 degradation via K48-linked polyubiquitination which subsequently suppresses the activation of downstream lipophagy signaling cascades in MASLD progression.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: Yaoyao Jin

LAB HEAD: Junyong Wang

PROVIDER: PXD076863 | Pride | 2026-05-30

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	XA06466B1DA_T46_1_Slot2-40_1_12719.d.zip	Other
	XA06466B1DA_T46_2_Slot2-41_1_12720.d.zip	Other
	XA06466B1DA_T46_3_Slot2-42_1_12721.d.zip	Other
	XA06466B1DA_Vec_1_Slot2-37_1_12715.d.zip	Other
	XA06466B1DA_Vec_2_Slot2-38_1_12716.d.zip	Other

Items per page:

1 - 5 of 8

Similar Datasets

Effects of D4-MASLD and D5-MASLD Diets on Rats: Pathway Alterations Similar to Human MASLD

Project description:Animal models are essential to understand the mechanisms underlying the onset and progression of metabolic associated steatotic liver disease (MASLD), a rapidly growing form of chronic liver disease driven largely by the global rise in metabolic syndrome. However, existing animal models for MASLD often fail to accurately reproduce advanced human liver disease, and have varying degrees of clinical relevance. To address this, we have undertaken efforts to create a dietary translational model of MASLD in rats that closely replicates the full MASLD phenotype observed in humans, including advanced fibrosis, portal hypertension, and metabolic syndrome. Three MASLD rat models were developed by sequentially combining a high-fat glucose-fructose diet (HFGFD) with additional factors: lipopolysaccharide, increased cholesterol (Chol), and cholic acid (CA) at different concentrations. Of these, two diets—D4-MASLD (HFGFD + 2% Chol) and D5-MASLD (HFGFD + 2% Chol + 0.1% CA)—effectively replicated MASLD characteristics. Transcriptomic analysis revealed that while both diets significantly altered gene expression compared to controls, D5-MASLD had a greater impact on the activation of inflammation and immune response pathways. The inclusion of CA in D5-MASLD exacerbated pathways related to microbiota changes, intestinal barrier dysfunction, and bacterial translocation. Additionally, comparison of the transcriptomic profiles of these diet-induced rat models with data from MASLD/MASH patients further validated the relevance of these models, establishing a robust platform for studying MASLD pathogenesis and evaluating potential therapeutic interventions.

2026-04-20 | GSE282001 | GEO

NSD2 aggravates metabolic dysfunction-associated steatotic liver disease progression by suppressing TFEB-mediated autophagy-lysosomal pathway

Project description:Extensive research has demonstrated that impaired autophagy contributes to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Qiao et al. identified NSD2 in the liver as a novel and essential regulator of MASLD. NSD2 epigenetically represses TFEB transcription through trimethylation of histone H4 at lysine 20 (H4K20me3), thereby impairing autophagic flux to exacerbate hepatic steatosis. In conclusion, NSD2 functions as a crucial epigenetic regulator of impaired autophagic flux in the liver, offering a novel therapeutic target for MASLD management.

2026-01-01 | GSE287554 | GEO

Intestinal organoid expression data from patients with MASLD-cirrhosis versus non-fibrotic MASLD

Project description:This study aimed to establish and characterize an in vitro model of human intestinal organoids isolated from duodenal samples of patients with non-fibrotic MASLD and those with MASLD-cirrhosis. Whole transcriptome analysis and the energetic and redox status of the organoids were assessed to characterize intestinal functional impairment in the context of MASLD. We used microarrays to detail the whole transcriptome dysregulation underlying intestinal dysfunction in organoids isolated from chirrotic versus non-fibrotic MASLD patients.

2025-09-04 | GSE299719 | GEO

Effects of D4-MASLD and D5-MASLD Diets on Rats: Pathway Alterations Similar to Human MASLD

Project description:Effects of D4-MASLD and D5-MASLD Diets on Rats: Pathway Alterations Similar to Human MASLD

| PRJNA1186599 | ENA

Allantoin promotes MASLD progression

Project description:Allantoin promotes MASLD progression

| PRJNA1194129 | ENA

Allantoin promotes MASLD progression

Project description:Uric acid has garnered increasing attention for its association with metabolic dysfunction-associated steatotic liver disease (MASLD) in recent cross-sectional studies, although detailed understanding of its involvement remains limited. This study confirms a strong association between urate levels and elevated risk of both MASLD and type 2 diabetes (T2D) through a large-scale observational analysis of UK Biobank data. However, Mendelian randomization (MR) analysis involving over 2 million samples identified only causal effects of urate on serum triglyceride levels and the risk of T2D. Additionally, a targeted metabolomics study involving elderly Chinese participants revealed that, rather than UA, allantoin—a byproduct of UA oxidation—was significantly elevated in individuals with dyslipidemia or T2D. Notably, a significant negative correlation was found between serum allantoin level and fasting glucose, as well as serum triglyceride and cholesterol levels. Animal studies demonstrated that allantoin exacerbates hepatic lipid accumulation and glucose intolerance in mice fed a high-fat diet, which was accompanied by increased hepatic lipid biogenesis and reduced bile acid production. Interestingly, our findings indicate that allantoin exhibits a strong binding affinity for PPARα, suggesting that it may act as an inhibitor of PPARα, thereby promoting the progression of MASLD. These results underscore the critical role of allantoin, rather than UA, in the development of MASLD, offering valuable insights for the prediction and management of hepatic metabolic disorders.

2025-06-04 | GSE283505 | GEO

RNA-seq data of primary human hepatocytes spheroids from healthy and Metabolic dysfunction associated steatotic liver disease (MASLD) donors following troglitazone treatment

Project description:Primary human hepatocytes from healthy and Metabolic dysfunction associated steatotic liver disease (MASLD) patients (6 donors each) as 3D spheroids treated with troglitazone (3 concentrations, 0.1xCmax, Cmax and 10xCmax) and vehicle for 7 h. Data for Figure 5 in connected publication.

2026-01-16 | E-MTAB-15610 | biostudies-arrayexpress

Effect of hepatocytic RKIP depletion on HFD-induced MASLD

Project description:High-fat diet (HFD) is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), yet the molecular pathways that connect dietary fats to liver dysfunction remain unclear. Hepatocyte-specific RKIP depletion in male mice exacerbates ER stress, resulting in lipid droplets accumulation and MASLD progression.

2025-09-03 | GSE300123 | GEO

The Mechanism by which HIF-2a Promotes MASLD

Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by imbalance of lipid metabolism and autoimmune inflammation. The relationship between Hypoxia-inducible Factor 2α (HIF-2α) and the progression of MASLD has been well-documented. However, the mechanistic linkage between HIF-2α and steatohepatitis progression remains largely elusive. Here, hepatocyte-specific HIF-2α knockout mice were used to identify underlying pathophysiological relevance in MASLD. Through multiple gain- and loss-of-function experiments in primary hepatocytes and established human hepatocyte cell lines to investigate the molecular mechanism of HIF-2α in MASLD progression. Compared to their wild-type littermates, hepatocyte-specific HIF-2α knockout mice exhibited a substantial reduction in hepatic steatosis and inflammatory pathway induced by high fat diet (HFD). Furthermore, the HIF-2ɑ deficiency in primary hepatocytes and both L02 and MIHA cell lines markedly inhibited the lipid accumulation, inflammation and endoplasmic reticulum stress in vitro under FFAs challenge. Mechanistically, HIF-2 directly bound to the promoter region of protein kinase RNA-like ER kinase (PERK), leading to the activation of the activating transcription Factor 4 (ATF4) signaling under metabolic stress, thereby aggravating lipogenesis while inhibiting lipid oxidation in hepatocytes.These data indicate that HIF-2α acts as a contributing factor to MASLD progression via ATF4 signaling.

2025-12-10 | GSE267155 | GEO

Transcriptomic profiling of NK cells in CHB and CHB-MASLD

Project description:Clinical evidence suggests that coexistence of metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic hepatitis B (CHB) is associated with more severe liver disease progression, but the underlying immune mechanisms remain incompletely understood. In this study, RNA sequencing was performed on peripheral natural killer (NK) cells isolated from patients with CHB and CHB-MASLD to characterize transcriptomic alterations associated with metabolic dysfunction. Differential expression and pathway analyses were used to identify immune activation programs and candidate signaling pathways linked to NK-cell remodeling in CHB-MASLD.

2026-06-17 | GSE325645 | GEO