Similar Datasets
Project description:Nonalcoholic Fatty Liver Disease (NAFLD) is a broad spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. The choline-deficient L-amino acid-defined (CDAA) diet-induced NAFLD animal model has traditionally been used to understand the molecular mechanisms of disease development and progression. Although this animal model shows a similar course of disease progression to human NAFLD, it does not develop comorbidities such as obesity and type 2 diabetes. Therefore, its relevance to human NAFLD (what aspects of the disease etiology are recapitulated in this model?) is not fully understood. We applied microarray analysis to characterize its pathophysiology, and evaluate the similarity across species.
2023-03-25 | GSE227714 | GEO
Project description:To investigate aldafermin-producting E.Coli Nissle 1917 effects in combination with dietary changes in NAFLD mouse model.
2023-10-31 | GSE232030 | GEO
Project description:Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the 2H2O-metabolic labeling approach to test the hypothesis that the reduced stability of oxidative phosphorylation proteins contributes to mitochondrial dysfunction in a diet-induced mouse model of NAFLD. A high fat diet containing cholesterol (a so-called Western diet (WD)) led to hepatic oxidative stress, steatosis, inflammation and mild fibrosis, all markers of NAFLD, in LDLR-/- mice. In addition, compared to controls, livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting reduced mitochondrial oxidative capacity. Proteome dynamics analysis revealed that mitochondrial dysfunction is associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41±0.46 vs. 5.15±0.49 day, P<0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome c oxidase subunit 4 isoform 1 of complex III (5.9 ± 0.1 vs 3.4 ± 0.8 day), ATP synthase subunit α (6.3±0.4 vs. 5.5±0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5±0.6 vs. 6.5±0.2 day) (P<0.05). These changes were associated with impaired complex III and F0F1-ATP synthase activities, suggesting that increased degradation of mitochondrial proteins contributed to hepatic mitochondrial dysfunction in NAFLD mice. Autophagy, but not proteasomal degradation, contributed to increased clearance of hepatic mitochondrial proteins in NAFLD mice. In conclusion, the proteome dynamics approach suggests that alterations in mitochondrial proteome dynamics is involved in hepatic mitochondrial dysfunction in NAFLD.
2018-11-21 | PXD008766 | Pride
Project description:The goal of this study was to determine the changes to cellular transcriptional programs following induction of intracellular lipid accumulation, with the aim of confirming the utility of this model for exploring mechanisms underlying the pathogenesis of NAFLD. Comparisons with other publically available data confirm that the alterations we observe in mRNA expression are similar to those observed in both humans and rodents.
2020-12-03 | GSE138052 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD), alongside the global obesity epidemic, is rapidly emerging as a dominant liver disease etiology that leads to progressive liver fibrosis, its terminal stage, cirrhosis, and hepatocellular carcinoma (HCC). We identified and validated a 133-gene signature (Prognostic Liver Signature for NAFLD [PLS-NAFLD]) to predict long-term HCC risk in patients with NAFLD. By analyzing PLS-NAFLD, IDO1 was identified as a potenial chemopreventive target for HCC from NAFLD. To test this hypothesis, we utilized our clinical-prognostic-signature-inducible cell culture model. We first confirmed that free fatty acid treatment (800 μM oleic acid and 400 μM palmitic acid) can induce PLS-NAFLD, then IDO1 inhibitor, epacadostat, can reverse the high-risk pattern in a dose-dependent manner.
2022-07-01 | GSE200460 | GEO
Project description:Despite some success in identifying CNVs responsible for metabolic phenotypes including obesity and diabetes mellitus, there are as yet no data available to suggest whether or not CNVs might be involved in the etiology of the NAFLD spectrum. This report is a comprehensive analysis of copy number in Malaysian patients with NAFLD. Genomic DNA was extracted from blood obtained from patients with NAFLD and submitted for genome-wide analysis using aCGH
2015-02-26 | E-GEOD-55645 | biostudies-arrayexpress
Project description:The mechanisms by which cholesterol promotes NAFLD remain far less clear. Animal models are necessary to explore the pathogenesis and therapies of NAFLD. Several previous studies have shown that pig breeds can differ in their metabolic phenotype in response to high-energy diet. To investigate whether genetic background has profound effects on pig NAFLD phenotype and their metabolic response to dietary cholesterol intake, we performed RNA-Seq on liver tissues from two miniature pig breeds fed either standard or a high-fat and high-cholesterol diet for 6 months.
2022-12-15 | GSE142346 | GEO
Project description:Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease (CVD). Liver is the major source of the circulatory proteins and alterations in plasma proteome have been implicated in atherosclerosis. We used a recently developed 2H2O-metabolic labeling method in combination with the label-free quantification to evaluate the effect of a Western diet (WD) on the dynamics of plasma proteins in LDL receptor-deficient (LDLR-/-) mice, a model of NAFLD and atherosclerosis. There were no significant changes in the expression level of total proteins due to the WD with a bulk protein mean half-life of 18.0±15.1 hours in control and 16.7±11.1 hours in WD groups. WD led to pro-inflammatory distribution of circulatory proteins analyzed in apoB-depleted plasma attributed to their increased production. The fractional catabolic rates of fast-turnover proteins with stress-response, lipid metabolism and transport functions were significantly increased with WD (P<0.05). The pathway analyses revealed that alterations in plasma proteome dynamics were related to the suppression of hepatic PPARα, which was confirmed based on reduced gene and protein expression of PPARα on WD. These changes were associated with ~4 fold increase (P<0.0001) in pro-inflammatory property of apoB-depleted plasma. In conclusion, the proteome dynamics method reveals pro-inflammatory remodeling of plasma proteome relevant to liver disease. As in vivo metrics of liver function, this approach can be used to test therapies in NAFLD and other diseases
2016-06-06 | PXD004270 | Pride