PINT MASLD Mouse Intervention HFD
Ontology highlight
ABSTRACT:
INSTRUMENT(S): 6540 Q-TOF LC/MS, Q Exactive Focus
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Kati Hanhineva
PROVIDER: MSV000099345 | MassIVE | Wed Oct 01 00:18:00 BST 2025
REPOSITORIES: MassIVE
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Project description:Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of hepatocellular carcinoma and liver transplantation worldwide, making identification of intervention strategies and therapeutic treatments essential to reducing morbidity and mortality associated with this disease. RNA binding proteins, like human antigen R (HuR), are ubiquitous and multi-faceted cell-stress regulators. HuR’s role in MASLD development is incompletely understood. This study aims to determine how hepatocyte HuR deficiency drives MASLD progression to Metabolic dysfunction-associated steatohepatitis (MASH). To model MASLD, we fed male hepatocyte-specific HuR knockout mice (HuRHep-/-) and WT control mice with the normal chow diet or the MASLD-inducing high fat, cholesterol, and fructose (HFCF) diet for 16 weeks. The liver transcriptomic profile was mapped using bulk RNA sequencing (RNA seq). After MASLD-inducing diet feeding, bile acid metabolism was modulated, while liver injury and fibrosis markers were increased in male HuRHep-/- mice, relative to WT. Our data suggests that hepatocyte HuR deficiency dysregulates bile acid metabolism and exacerbates MASLD progression.
2026-06-03 | GSE287727 | GEO
Project description:Although maternal obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the pathogenesis remains unclear. We aimed to evaluate the effect and mechanisms of multigenerational maternal western diet (WD) on MASLD progression, and test drug candidates in a preclinical model. Female mice were fed WD from 8 weeks before breeding initiation with a normal chow (NC)-fed male, throughout pregnancy and lactation. Male offspring were weaned onto NC or WD and assessed at the age of 16 weeks. Maternal WD feeding aggravated body weight gain, insulin resistance, steatosis and inflammation. Fibrosis was only observed in offspring exposed to maternal WD. Mechanistically, the latter exhibited reduced OXPHOS activity. Maternal WD aggravates MASLD in male offspring, with mitochondrial dysfunction contributing to disease severity.
2025-06-18 | GSE291363 | GEO
Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (rosiglitazone, pioglitazone, T0901317, or salicylate) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks).
2014-05-14 | GSE57659 | GEO
Project description:The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Considering the fact that MASLD patients accompanying type 2 diabetes mellitus (T2DM) have high risk of developing metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, and HCC, we treated low-dose streptozotocin (STZ; 40 mg/kg) for 5 consecutive days and subsequently fed a high-fat diet (HFD) to male C57BL/6J mice at 7 weeks of age (STZ+HFD). STZ+HFD mice gradually developed fatty liver, MASH, hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. In particular, from 20 weeks of age, MASH was evident, and from 32 weeks of age, advanced fibrosis was developed. At 38 weeks, a proportion of STZ+HFD mice developed HCC, which was subsequently observed in all mice up to 68 weeks of age. Furthermore, the hepatic transcriptomic features of STZ+HFD mice closely reflected those of obese patients with T2DM, MASH and MASLD-related HCC. Notably, dietary changes and tirzepatide administration alleviated MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ+HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients with metabolic dysfunction was successfully established.
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Project description:To identify potential role of macrophage LPCAT3 in progression of hepatic steatosis in mice, we isolated Kupffer cells from mice deficient for LPCAT3 in macrophages and fed a high fat diet for 16 weeks
2021-03-01 | GSE146004 | GEO
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread chronic liver disorder spanning simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Suitable animal models are crucial for therapeutic development, yet many fail to reproduce progression to fibrosing MASH. Here, we employed the STAM model in male C57BL/6J mice to simulate MASLD and investigated whether a high-fat, high-cholesterol (HFHC) diet would intensify disease progression compared with the standard high-fat (HF) diet. HFHC feeding in the STAM model accelerated hepatic lipid accumulation, crown-like structure formation, inflammation, and fibrosis, as demonstrated by histological analyses. Transcriptomic profiling and pathway enrichment confirmed activation of lipid and cholesterol metabolism, regulation of TNF production, and inflammatory signaling. Reactome analysis further indicated alterations in extracellular matrix formation and immune system pathways, consistent with advanced fibrotic progression. In summary, integration of HFHC feeding with the STAM model produced a more severe liver phenotype that better mirrors the pathological spectrum of MASLD.
2026-03-19 | GSE319011 | GEO
Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (metformin, glibenclamide, sitagliptin, rosiglitazone, pioglitazone, fenofibrate, T0901317, atorvastatin, salicylate or rofecoxib) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks).
2013-04-18 | E-MTAB-1063 | biostudies-arrayexpress
Project description:This study sought to interrogate the effects of lipids and lipid metabolites on the hepatic proteome. Protein expression in high-fat diet (HFD) mouse livers vs. livers of normal chow fed (NC) mice were investigated using multiplexed quantitative LC-MS/MS (TMT labeling). This experiment contains additional replicates for normal chow and mice on high-fat diet for 16 weeks.
2019-07-08 | PXD013815 | Pride
Project description:Accumulating evidence suggests that a compromised intestinal epithelial barrier (IEB) contributes to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the exact mechanisms remain unclear. Here we reveal that intestinal mucin 1 (MUC1) levels and glycosylation are decreased in both humans and mice with MASLD. Enterocyte-specific Muc1 knockout aggravates high-fat diet (HFD)-induced IEB impairment and MASLD progression in mice. Mechanistically, HFD feeding reduces the glycosylation of intestinal epithelial MUC1, triggering its clathrin-mediated endocytosis and NEDD4-mediated lysosomal degradation, which subsequently induces β-Catenin degradation and ultimately impaires the IEB. Notably, enterocyte-specific overexpression of cytoplasmic-tail-deleted MUC1 protects against IEB impairment and mitigates MASLD progression. These findings indicate that reduced intestinal epithelial MUC1 levels facilitate the progression of MASLD. Preserving the glycosylation and levels of intestinal MUC1 to maintain IEB integrity is a potential therapeutic strategy to explore for MASLD.
2025-12-14 | PXD066810 | Pride
Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (rosiglitazone, pioglitazone, T0901317, or salicylate) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks). One group (n=9) remained on maintenance chow throughout the entire study period (16 weeks) and served as healthy, age-matched control. After the nine week run-in period, the HFD fed mice were matched into thirteen groups based on body weight. The first group (n=9) was sacrificed immediately after matching. The second group (n=15) was continued on HFD until the end of the experiment at t=16 weeks. The fourth group (n=9) was switched to regular chow (dietary lifestyle intervention). The other groups (each n=9) continued on HFD supplemented with drugs typically used in clinical practice. More specifically, following drugs were mixed into HFD ; rosiglitazone (0.010% w/w), pioglitazone (0.010% w/w), T0901317 (0.010% w/w) and salicylate (0.40% w/w).
2014-05-14 | E-GEOD-57659 | biostudies-arrayexpress