Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA240195 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient (MCD) + high fat (HF) diet with or without 0.1% metformin for 8 weeks.
2012-02-21 | E-GEOD-35961 | biostudies-arrayexpress
Project description:The microRNAs expression was markedly altered with the MCD diet. Using a custom microarray platform, we analyzed the expression levels of 1135 mouse microRNA probes in liver tissue that were fed MCD diet.
2015-03-01 | E-GEOD-55593 | biostudies-arrayexpress
Project description:Kupffer cells (KCs) self-renew by local proliferation in the adult independently from monocytes (Mos). However, how they maintain during chronic metabolic disorders such as non-alcoholic steatohepatitis (NASH) remains ill-defined. We characterized KCs during NASH and observed diversity in the KC pool, with a significant fraction of monocyte-derived KCs (MoKCs). Here, we aim to uncover the transcriptional landscapes of KCs subsets found in a mouse model of methionine and choline deficient (MCD)-diet induced non-alcoholic steatohepatitis (NASH).
2020-12-04 | GSE138778 | GEO
Project description:Study of microRNA associated with metformin treatment in a mouse model of NASH(MCD)
| PRJNA240192 | ENA
Project description:Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease, is one of the leading causes of liver disease worldwide and may further progress to cirrhosis and cancer. However, the pathogenesis of NASH remains unclear, and there is currently only one FDA-approved drug for its treatment; therefore, new therapeutic approaches are urgently needed. Under high-fat diet or obese conditions, PPARγ is activated in the liver to promote lipid storage as droplets, inducing the progression of NASH. We showed that the expression level of USP28 is elevated in the livers of NAFLD/NASH patients. Through dietary induction, including a methionine-choline deficient (MCD) diet and a Western diet (WD) combined with intraperitoneal injection of carbon tetrachloride (CCl4), we established two severe mouse models of NASH and revealed the role of the deubiquitinase USP28. Mechanistically, the hepatic deubiquitinase USP28 directly binds to PPARγ and prevents its own ubiquitination and degradation, thereby regulating its downstream signaling pathways. In the absence of Usp28 or if the DUB is inhibited, PPARγ is downregulated, and the PPAR signaling pathway is inhibited, allowing the cells to mount a defensive response to excessive fat. Both genetic and pharmacological inactivation of Usp28 significantly attenuated the NASH phenotype induced by the MCD diet or WD-CCl4 regimen, as well as WD-CCl4-induced hepatocellular carcinoma in mice.
2025-04-23 | GSE268120 | GEO
Project description:Recent studies have revealed the pivotal role of gut microbiota in the precession of liver diseases including non-alcoholic steatohepatitis (NASH). Many natural herbs, such as Gynostemma pentaphyllum (GP), have been extensively used applied in the treatment prevention of NASH, while the bioactive components and underlying mechanism remain unclear. The aim of this study was to investigate whether the polysaccharides of GP (GPP) has the protective effect on of NASH and to explore the potential mechanism underlying these effects. To investigate the function high dose of GPP(HGPP) in the regulation of hepatic gene expression, C57BL/6 male mice were fed with methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH, and administered daily oral gavage of the sodium carboxymethylcellulose (CMC-Na) for model group, HGPP for experimental group, compared with normal control methionine-choline-sufficient (MCS) group.
2022-06-16 | GSE205974 | GEO
Project description:Non-alcoholic steatohepatitis (NASH) is a fatty liver disease that does not involve alcohol consumption and is characterized by fatty degeneration, inflammation, and hepatocellular damage. Therefore, predicting future fibrosis is necessary in the early stages of NASH to prevent developing diseases. This study examined histological changes in the liver as well as microRNA expression changes in the liver and serum of NASH mice model to search for potential biomarker candidates that may predict early fibrosis. This study used 6-week-old C57BL/6NJcl male mice and fed the control and NASH groups with a food-breeding solid diet (CE-2) and a high-fat diet (choline-deficient high-fat and 0.1% [w/v] methionine supplemented diet), respectively. We used Agilent Technologies miRNA microarray to examine microRNA expression in the liver and serum.
2024-01-31 | GSE252035 | GEO
Project description:The aim of the current study was to check whether chronic treatment with AN1284 could reverse steatosis and fibrosis in a mouse model of NASH. We used a mouse model of dietary induced NASH that was given for 4 month. Treatment with saline or AN1284 was given via implanted minipumps for 2 month. Treatment was started after 2 month feeding. Our results revealed that AN1284 significantly attenuated liver damage, as indicated by a reduced liver/body ratio, decreased ALT serum levels, a significant reduction in liver fat content and hepatic fibrosis. To investigate the underlying mechanism, we performed RNA sequencing on mice fed with normal diet (ND) or high fat diet (HFD; Envigo-Teklad TD.150235).
2023-08-16 | GSE186116 | GEO
Project description:Nonalcoholic steatohepatitis (NASH) might soon become the leading cause of end-stage liver disease worldwide with limited treatment options. Liver fibrosis, driven by chronic inflammation and hepatic stellate cells (HSCs) activation, critically determines morbidity and mortality in patients with NASH. Pyruvate kinase M2 (PKM2) is involved in immune activation and inflammatory liver diseases; however, its role and therapeutic potential in NASH fibrosis remain largely unexplored. By bioinformatic screening and analysis of human and murine NASH livers, we found that PKM2 was specifically upregulated in non-parenchymal cells (NPCs) in fibrotic NASH livers, especially in macrophages. Macrophage-specific Pkm2 knockout (Pkm2fl/flLysMCre) significantly ameliorated hepatic inflammation and fibrosis severity in three distinct NASH models induced by methionine–choline-deficient (MCD) diet, high-fat high-cholesterol (HFHC) diet and western diet plus weekly carbon tetrachloride injection (WD/CCl4). Single-cell transcriptomic analysis indicated that deletion of PKM2 in macrophage reduced profibrotic Ly6Chigh macrophage infiltration. Mechanistically, PKM2-dependent glycolysis promotes NLRP3 activation in proinflammatory macrophages, thus inducing HSCs activation and fibrogenesis. Pharmacological PKM2 agonist efficiently attenuated the profibrotic crosstalk between macrophages and HSCs in vitro and in vivo. Translationally, ablation of PKM2 in NPCs by cholesterol-conjugated heteroduplex oligonucleotides, a novel oligonucleotide drug that preferentially accumulated in the liver, dose-dependently reversed NASH fibrosis without observable hepatotoxicity. Our study highlights the pivotal role of macrophage PKM2 in advancing NASH fibrogenesis. Therapeutic modulation of PKM2 in a macrophage-specific or liver-specific fashion may serve as a novel strategy to combat NASH fibrosis.
2024-05-08 | GSE266040 | GEO