Characteristics of liver tissues of MASH compared to those of Simple Steatosis mice.
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PROVIDER: PRJNA1260808 | ENA |
REPOSITORIES: ENA
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Project description:Characteristics of hepatocytes of Metabolic Dysfunction-Associated Steatohepatitis (MASH) mice were compared compared to those of Simple Steatosis (SS) mice in the context of UPR response.
2025-06-19 | GSE296715 | GEO
Project description:Background & aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) ranges from simple steatosis (MAFL) to metabolic dysfunction-associated steatohepatitis (MASH). With the complex etiological factors associated with MAFLD, the molecular mechanism underlying the progression from steatosis to MASH has not been fully elucidated, resulting in a limited number of effective therapeutic interventions. Methods: We examined the profiling changes of MicroRNAs (miRNAs) in vivo and in vitro experiments and miR - 300 - 3p was identified as a crucial checkpoint in this process in the current experiments. The present studies were carried out to explore the role of miR - 300 - 3p in the advancement of MASH. Bioinformatic analysis, RNA - Sequencing, and dual - luciferase reporter assays were used to investigate the might target of miR - 300 - 3p. Results: We investigated the profiling changes of miRNA and identified miR - 300 - 3p is low expressed in mouse experiments and HepG2 cells. In vitro loss of function study revealed that suppression of miR - 300 - 3p in steatotic HepG2 cells could induce obvious inhibit cell autophagy, promote cell apoptosis, cause lipid accumulation, hepatic inflammation and injury, which are the primary characteristics within the pathology of MASH. STX17 was a predicted target gene of miR-300-3p through RNA-Sequencing, bioinformatic analysis and dual-luciferase reporter assays. Downregulation miR-300-3p was able to downregulate STX17 to promotes steatosis-to-MASH progression. In contrast, transduction of miR - 300 - 3p and over-STX17 inhibit steatosis-to_x0002_MASH progressionin. The results was inconsistent with canonical miRNA biology predicts, which indicated that the regulation of miR - 300 - 3p on STX17 might has context-dependent and involve indirect mechanism, feedback loop or multi-level control. Potentially clinically significant, the miR - 300 - 3p/STX17 regulatory axis has also been confirmed in human plasma. Expression level of miR - 300 - 3p and STX17 was reduced in plasma of MAFLD patients. Their expression levels were closely related to liver biochemical indicators and lipid profile indicators. Conclusion: Our research results highlight the function of the miR - 300 - 3p/ STX17 regulatory axis in the progression from steatosis to MASH. This suggests that either the supplementation of miR - 300 - 3p or STX17 may provide a promising therapeutic strategy for treating MASH in hepatocytes. The underlying mechanism through which miR - 300 - 3p regulates STX17 requires further investigation.
2026-05-20 | GSE328114 | GEO
Project description:Liver Transcriptomes of Simple steatosis in Mice
| PRJNA818539 | ENA
Project description:In our study, we constructed a Simple steatosis (NAFL) mouse model with a high-fructose and high-cholesterol (HFHC diet) for 12 weeks. Next, we performed RNA Sequencing analysis to reveal molecular features of Simple steatosis. As a result, we obtained hepatic genome-wide mRNA expression in the livers from two groups of mice (NAFL versus Normal).Using FDR < 0.01 and fold change > 2 as the threshold, we identified 176 differentially expressed genes (DEGs) in the livers of NAFL mice relative to the normal control mice, of which 118 up-regulated and 58 down-regulated. The top 5 up-regulated genes in NAFL mice included the genes encoding for Themis, Cfd, Aqp8, Osbpi3 and Scd1.
2022-03-25 | GSE199121 | GEO
Project description:Background & Aims: Fibrosis drives liver-related mortality in metabolic dysfunction-associated steatohepatitis (MASH), yet we have limited medical therapies to target MASH-fibrosis progression. Here we report that mannose, a simple sugar, attenuates MASH steatosis and fibrosis in two robust murine models and human liver slices. Methods: The well-validated FAT-MASH murine model for liver steatosis and fibrosis was employed. Mannose was supplied in the drinking water at the start (“Prevention” group) or at week 6 of the 12-week MASH regimen (“Therapy” group). The in vivo anti-fibrotic effects of mannose supplementation were tested in a second model of carbon tetrachloride (CCl4)-induced liver fibrosis. A quantitative and automated digital pathology approach was used to comprehensively assess steatosis and fibrosis phenotypes. Mannose was also tested in vitro in human and primary mouse hepatocytes conditioned with free fatty acids alone or with fructose, and Human Precision Cut Liver Slices (hPCLS) from patients with end-stage MASH cirrhosis. Results: Oral mannose supplementation improved liver fibrosis in vivo in both FAT-MASH and CCl4 mouse models, as well as in hPCLS MASH samples. Mannose also reduced liver steatosis in FAT-MASH mice, and in human and mouse hepatocytes in vitro. Ketohexokinase (KHK), the main enzyme in fructolysis, was decreased with mannose in whole mouse liver, cultured hepatocytes, and hPCLS. Removal of fructose or overexpression of KHK each abrogated the anti-steatotic effects of mannose. Conclusions: This study identifies mannose as a novel therapeutic candidate for MASH that mitigates steatosis by dampening hepatocyte KHK expression and exerts independent anti-fibrotic effects in two mouse models and human liver tissue slices.
2025-01-31 | GSE287943 | GEO
Project description:Through mass spectrometry, we quantified liver global proteomes of Simple steatosis and Non-alcoholic Steatohepatitis in a HFHC diet induced mouse model
2022-03-24 | PXD032806 |
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.
2025-04-14 | PXD052784 | Pride
Project description:The circadian clock synchronizes physiological processes with the 24-hour light-dark cycle. Clock disruption contributes to metabolic disorders, including metabolic dysfunction-associated steatohepatitis (MASH). Here, we investigated the role of the hepatocyte clock in MASH using hepatocyte-specific Bmal1 deletion (Hep-Bmal1KO) mice. Hep-Bmal1KO mice showed faster MASH progression with increased hepatic cholesterol, inflammation, and fibrosis. Transcriptomic and lipidomic analyses revealed dysregulated cholesterol metabolism in Hep-Bmal1KO mice, marked by reduced expression and disrupted rhythmicity of key cholesterol-related genes. Bioinformatic analyses identified Chrebp as a potential co-regulator of these transcriptional changes. In an in vitro model with palmitate exposure and gene silencing, we found that Bmal1, but not Chrebp, regulated cholesterol accumulation, indicating Bmal1’s specific role in hepatic cholesterol metabolism. Translating our findings to a human patient cohort revealed a significantly shifted circadian phase, despite no marked effect on hepatic cholesterol levels in the livers of patients with more advanced liver disease (i.e., MASH) compared to simple steatosis. Taken altogether, our findings offer a roadmap to understand the hepatocyte clock's role in MASH and its potential as a therapeutic target.
2026-05-28 | GSE304692 | GEO
Project description:The circadian clock synchronizes physiological processes with the 24-hour light-dark cycle. Clock disruption contributes to metabolic disorders, including metabolic dysfunction-associated steatohepatitis (MASH). Here, we investigated the role of the hepatocyte clock in MASH using hepatocyte-specific Bmal1 deletion (Hep-Bmal1KO) mice. Hep-Bmal1KO mice showed faster MASH progression with increased hepatic cholesterol, inflammation, and fibrosis. Transcriptomic and lipidomic analyses revealed dysregulated cholesterol metabolism in Hep-Bmal1KO mice, marked by reduced expression and disrupted rhythmicity of key cholesterol-related genes. Bioinformatic analyses identified Chrebp as a potential co-regulator of these transcriptional changes. In an in vitro model with palmitate exposure and gene silencing, we found that Bmal1, but not Chrebp, regulated cholesterol accumulation, indicating Bmal1’s specific role in hepatic cholesterol metabolism. Translating our findings to a human patient cohort revealed a significantly shifted circadian phase, despite no marked effect on hepatic cholesterol levels in the livers of patients with more advanced liver disease (i.e., MASH) compared to simple steatosis. Taken altogether, our findings offer a roadmap to understand the hepatocyte clock's role in MASH and its potential as a therapeutic target.
2026-05-28 | GSE304691 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a severe chronic liver condition characterized by hepatocyte steatosis, inflammation and fibrosis, with a rising prevalence globally, posing significant health risks and potentially leading to complications such as cirrhosis, liver failure, and increased mortality. Previous study in our lab has identified Themis as a highly up-regulated gene in hepatocytes during MASH progression using a diet-induced mouse model. Genetic ablation of Themis exacerbated MASH symptoms, including more severe steatosis, liver injury, fibrosis and more immune cell infiltration.
2026-02-10 | GSE300143 | GEO