Project description:Non–alcoholic fatty liver disease (NAFLD) is high prevalent in worldwide and associated with chronic kidney disease (CKD). Infection with Opisthorchis viverrini (Ov) infection and consumption of high fat and high fructose (HFF) exacerbates NAFLD to nonalcoholic steatohepatitis in hamsters. Here, we aimed to investigate the effect a combination of HFF diet and Ov infection on kidney pathology via alteration of gut microbiome and proteome in hamster.
Project description:Mardinoglu2014 - Genome-scale metabolic model
(HMR version 2.0) - human hepatocytes (iHepatocytes2322)
This model is described in the article:
Genome-scale metabolic
modelling of hepatocytes reveals serine deficiency in patients
with non-alcoholic fatty liver disease.
Mardinoglu A, Agren R, Kampf C,
Asplund A, Uhlen M, Nielsen J.
Nat Commun 2014; 5: 3083
Abstract:
Several liver disorders result from perturbations in the
metabolism of hepatocytes, and their underlying mechanisms can
be outlined through the use of genome-scale metabolic models
(GEMs). Here we reconstruct a consensus GEM for hepatocytes,
which we call iHepatocytes2322, that extends previous models by
including an extensive description of lipid metabolism. We
build iHepatocytes2322 using Human Metabolic Reaction 2.0
database and proteomics data in Human Protein Atlas, which
experimentally validates the incorporated reactions. The
reconstruction process enables improved annotation of the
proteomics data using the network centric view of
iHepatocytes2322. We then use iHepatocytes2322 to analyse
transcriptomics data obtained from patients with non-alcoholic
fatty liver disease. We show that blood concentrations of
chondroitin and heparan sulphates are suitable for diagnosing
non-alcoholic steatohepatitis and for the staging of
non-alcoholic fatty liver disease. Furthermore, we observe
serine deficiency in patients with NASH and identify PSPH,
SHMT1 and BCAT1 as potential therapeutic targets for the
treatment of non-alcoholic steatohepatitis.
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MODEL1402200003.
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2005-01-01 | MODEL1402200003 | BioModels
Project description:Gut microbiome of non-alcoholic fatty liver disease
Project description:High-calorie diets lead hepatic steatosis and to the development of non-alcoholic fatty liver disease (NAFLD), which can evolve over many years into the inflammatory form non-alcoholic steatohepatits (NASH) posing a risk for the development of hepatocellular carcinoma (HCC). Due to the diet and the liver alteration, the axis between liver and gut is disturbed, resulting in gut microbiome alterations. Consequently, detecting these gut microbiome alterations repre-sents a promising strategy for early NASH and HCC detection. We analyzed medical parame-ters and the fecal metaproteome of 19 healthy controls, 32 NASH, and 29 HCC patients target-ing the discovery of diagnostic biomarkers. Here, NASH and HCC resulted in increased in-flammation status and shifts within the composition of the gut microbiome. Increased abun-dance of kielin/chordin, E3 ubiquitin ligase, and nucleophosmin 1 represented valuable fecal biomarkers indicating disease-related changes in the liver. Whereas a single biomarker failed to separate NASH and HCC, machine learning-based classification algorithms provided 0.86% accuracy in distinguishing between controls, NASH, and HCC. Conclusion: Fecal metaproteomics enables early detection of NASH and HCC by providing single biomarkers and ma-chine learning-based metaprotein panels.
2022-10-13 | PXD034175 | Pride
Project description:Gut microbiome analysis in patients with non-alcoholic fatty liver disease
Project description:Non-alcoholic fatty liver disease (NAFLD) influence one of third population around the world. Until now, no effective treatments have been established due to the improper in vitro assays and experimental animal models. By co-culturing human gut and liver cell lines (CaCO2 and HepG2 cells, respectively) interconnected via the microfluidic closed medium circulation loop, we created a gut-liver-on-a-chip (iGLC) platform as an in vitro human model of the gut-liver axis (GLA) in initiation and progression of NAFLD.
Project description:Non-alcoholic fatty liver disease (NAFLD) influence one of third population around the world. Until now, no effective treatments have been established due to the improper in vitro assays and experimental animal models. By co-culturing human gut and liver cell lines (CaCO2 and HepG2 cells, respectively) interconnected via the microfluidic closed medium circulation loop, we created a gut-liver-on-a-chip (iGLC) platform as an in vitro human model of the gut-liver axis (GLA) in initiation and progression of NAFLD.
Project description:Hepatic steatosis is the initial manifestation of abnormal liver functions and often leads to liver diseases such as non-alcoholic fatty liver disease in humans and fatty liver syndrome in animals. In this study, we conducted a comprehensive analysis of a large chicken population consisting of 705 adult hens by combining host genome resequencing, liver transcriptome, proteome, and metabolome analysis, as well as microbial 16S rRNA gene sequencing of each gut segment.