Cyclo (His-Pro): a further step in the prevention of steatohepatitis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA962499 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24339300_1.fastq.gz | Fastqsanger.gz | |||
| SRR24339300_2.fastq.gz | Fastqsanger.gz | |||
| SRR24339301_1.fastq.gz | Fastqsanger.gz | |||
| SRR24339301_2.fastq.gz | Fastqsanger.gz | |||
| SRR24339302_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Cyclo(His-Pro): A further step in the management of steatohepatitis
| PRJNA826474 | ENA
Project description:Cyclo(His-Pro): A further step in the management of steatohepatitis
| PRJNA893223 | ENA
Project description:Non-alcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease in the world, and despite this has no approved therapy. The naturally occurring compound Cyclo (His-Pro) (CHP) has been described as having anti-inflammatory and hypoglycemic properties. We show that CHP administration in a mouse model of NAFLD/NASH protects against disease progression. Based on our study, CHP prevents overall lipid accumulation, reducing body weight and fat mass. The treatment lowers systemic inflammation and prevents the development of insulin resistance. Specifically, the effect of CHP in the liver is remarkable, it reduces the steatosis while preventing inflammation and fibrosis, typical features of NADLF/NASH progression. The analysis of the liver transcriptome underscores the anti-fibrotic and anti-inflammatory effects of the treatment, supported by histology results. CHP, which has an excellent safety record, may hence represent a novel approach to manage NAFLD.
2023-08-14 | GSE230745 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is now considered the most common liver disease in the world, yet no pharmacological treatment has been approved. The naturally occurring compound Cyclo (His-Pro) (CHP) appears as an interesting candidate for the management of NAFLD, given its safety records and its anti-inflammatory effect. We show here that CHP administration protects against progression towards steatohepatitis (NASH) and fibrosis in two different mouse models of liver injury: a model of dietary NAFLD/NASH, achieved with thermoneutral housing in combination with a western diet, and a model of liver fibrosis by repeated injections with carbon tetrachloride. CHP administration prevents overall lipid accumulation, reducing body weight and fat mass. Treated animals show lower systemic inflammation and improved glycemia. Histo-pathology and liver transcriptomics highlight reduced steatosis upon CHP, together with lower inflammation and fibrosis, which are typical features of NAFLD progression. For the first time, we identified ERK as an early mediator of CHP response, although more work is required to elucidate its precise mechanism of action. In conclusion, our work indicates that CHP is a novel and efficacious strategy to manage NAFLD, fuelling optimism for potential clinical studies.
2023-08-14 | GSE216366 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease in the world, and despite this has no approved therapy. The naturally occurring compound Cyclo (His-Pro) (CHP) has been described as having anti-inflammatory and hypoglycemic properties. We show that CHP administration in a mouse model of NAFLD/NASH protects against disease progression. Based on our study, CHP prevents overall lipid accumulation, reducing body weight and fat mass. The treatment lowers systemic inflammation and prevents the development of insulin resistance. Specifically, the effect of CHP in the liver is remarkable, it reduces the steatosis while preventing inflammation and fibrosis, typical features of NADLF/NASH progression. The analysis of the liver transcriptome underscores the anti-fibrotic and anti-inflammatory effects of the treatment, supported by histology results. CHP, which has an excellent safety record, may hence represent a novel approach to manage NAFLD.
2023-08-14 | GSE200750 | GEO
Project description:Background & aimsNon-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) have become the world's most common liver diseases, placing a growing strain on healthcare systems worldwide. Nonetheless, no effective pharmacological treatment has been approved. The naturally occurring compound cyclo histidine-proline (His-Pro) (CHP) is an interesting candidate for NAFLD management, given its safety profile and anti-inflammatory effects.MethodsTwo different mouse models of liver disease were used to evaluate protective effects of CHP on disease progression towards fibrosis: a model of dietary NAFLD/NASH, achieved by thermoneutral housing (TN) in combination with feeding a western diet (WD), and liver fibrosis caused by repeated injections with carbon tetrachloride (CCl4).ResultsTreatment with CHP limited overall lipid accumulation, lowered systemic inflammation, and prevented hyperglycaemia. Histopathology and liver transcriptomics highlighted reduced steatosis and demonstrated remarkable protection from the development of inflammation and fibrosis, features which herald the progression of NAFLD. We identified the extracellular signal-regulated kinase (ERK) pathway as an early mediator of the cellular response to CHP.ConclusionsCHP was active in both the preventive and therapeutic setting, reducing liver steatosis, fibrosis, and inflammation and improving several markers of liver disease.Impact and implicationsConsidering the incidence and the lack of approved treatments, it is urgent to identify new strategies that prevent and manage NAFLD. CHP was effective in attenuating NAFLD progression in two animal models of the disease. Overall, our work points to CHP as a novel and effective strategy for the management of NAFLD, fuelling optimism for potential clinical studies.
| S-EPMC10432811 | biostudies-literature
Project description:HIS susceptibility in Swiss pigs
| PRJEB62539 | ENA
Project description:Pathogenesis and factors for determining progression of alcoholic and non-alcoholic steatosis to steatohepatitis with risk of further progression to liver cirrhosis and cancer are poorly understood. In the present study, we aimed to identify potential molecular signatures for discrimination of steatohepatitis from steatosis. Global gene expression analysis was applied to unravel differentially expressed genes between steatohepatitis compared to steatosis and control samples. For functional annotation as well as the identification of disease-relevant biological processes of the differentially expressed genes the gene ontology (GO) database was used. Genes down-regulated in steatohepatitis were mainly involved in metabolic processes. Genes up-regulated in steatohepatitis samples were associated with cancer progression and proliferation. Further statistical and pathway analysis lead to the selection of 46 candidate genes which were validated in two sample cohorts by quantitative real-time PCR. In surgical liver resection samples 39 genes and in percutaneous liver biopsies 30 genes were significantly up-regulated in steatohepatitis. Conclusion: The development of steatohepatitis is characterized by distinct molecular changes. 44 human liver tissue surgical samples (normal n=13; steatosis n=19; steatohepatitis n=12, 8/2 cirrhotic/non-cirrhotic) obtained from patients undergoing liver surgery for HCC, other malignancy/metastatic disease, benign tumors of the liver and organ dedicated to transplantation. Virtually normal control samples in this cohort were taken from patients undergoing surgical resection of liver metastasis, but the surrounding liver tissue used for the molecular analyses was normal, non-tumorous liver tissue without detectable pathological changes. The samples were provided by the Biobank at the Medical University of Graz. This dataset is part of the TransQST collection.
2012-12-10 | E-GEOD-33814 | biostudies-arrayexpress
Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.
2013-04-02 | E-GEOD-37031 | biostudies-arrayexpress