Identification of key metabolic changes during liver fibrosis progression in rats using a urine and serum metabolomics approach

Chang, Hong; Meng, Hongyu; Liu, Shumin; Wang, Yu; Yang, Xiaoxu; Lü, Fang; Wang, Hongyu

doi:10.1038/s41598-017-11759-z

Cited by 80 publications

(54 citation statements)

References 44 publications

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“…The processed datasets analysed by principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) (Trygg et al 2007) using pareto (Par) scaling. VIP (Variable Importance in the Projection) and p(corr) were used (V-Plot) to find statistically changed ions (Chang et al 2017). Ions with VIP > 1.5 and p(corr) > |0.4| were subjected to univariate analysis with False Discovery Rate (FDR) at 5% level for correction of multiple comparisons using Prism v.7 (Graph Pad, San Diego, California, USA).…”

Section: Lipidomics Data Analysismentioning

confidence: 99%

Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis

et al. 2020

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Introduction Osteoarthritis (OA) is the most common form of joint disease, causing pain and disability. Previous studies have demonstrated the role of lipid mediators in OA pathogenesis. Objectives To explore potential alterations in the plasma lipidomic profile in an established mouse model of OA, with a view to identification of potential biomarkers of pain and/or pathology. Methods Pain behaviour was assessed following destabilisation of the medial meniscus (DMM) model of OA (n = 8 mice) and compared to sham controls (n = 7). Plasma and knee joints were collected at 16 weeks post-surgery. Plasma samples were analysed using ultra-high performance liquid chromatography accurate mass high resolution mass spectrometry (UHPLC-HR-MS) to identify potential differences in the lipidome, using multivariate and univariate statistical analyses. Correlations between pain behaviour, joint pathology and levels of lipids were investigated. Results 24 lipids, predominantly from the lipid classes of cholesterol esters (CE), fatty acids (FA), phosphatidylcholines (PC), N-acylethanolamines (NAE) and sphingomyelins (SM), were differentially expressed in DMM plasma compared to sham plasma. Six of these lipids which were increased in the DMM model were identified as CE(18:2), CE(20:4), CE(22:6), PC(18:0/18:2), PC(38:7) and SM(d34:1). CEs were positively correlated with pain behaviour and all six lipid species were positively correlated with cartilage damage. Pathways shown to be involved in altered lipid homeostasis in OA were steroid biosynthesis and sphingolipid metabolism. Conclusion We identify plasma lipid species associated with pain and/or pathology in a DMM model of OA.

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Section: Lipidomics Data Analysismentioning

confidence: 99%

Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis

et al. 2020

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“…The fact that non‐responders showed lower NEFA levels, may reflect a lesser β‐adrenergic stimulation or a metabolic resistance of the β‐adrenoceptor that might explain that NSBB did not reach the desired effect. Glycerophospholipids have been proposed as protective agents in animal models of NASH and declining levels have been described in parallel to liver fibrosis progression . Therefore, it might be hypothesized that lower levels of glycerophospholids observed in HVPG non‐responders might be related to a more fibrogenic phenotype of cirrhosis, which could be less dependent and modifiable by vasoactive systems such as β‐adrenergic stimulation/blockade.…”

Section: Discussionmentioning

confidence: 99%

“…Glycerophospholipids have been proposed as protective agents in animal models of NASH and declining levels have been described in parallel to liver fibrosis progression. 35,36 Therefore, it might be hypothesized that lower levels of glycerophospholids observed in HVPG non-responders might be related to a more fibrogenic phenotype of cirrhosis, which could be Seventeen patients fell in the grey zone patients with cirrhosis. The analysis of these metabolites could be a useful non-invasive tool to identify these patients though further validation of the model would be desirable.…”

Section: F I G U R E 1 Heatmap Of Individual Metabolites At Differentmentioning

confidence: 99%

Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis

Reverter

Lozano

Alonso

et al. 2019

Liver International

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Background In cirrhosis, a decrease in hepatic venous pressure gradient (HVPG) > 10% after acute iv propranolol (HVPG response) is associated with a lower risk of decompensation and death. Only a part of patients are HVPG responders and there are no accurate non‐invasive markers to identify them. We aimed at discovering metabolomic biomarkers of HVPG responders to propranolol. Methods Sixty‐six patients with cirrhosis and HVPG ≥ 10 mm Hg in whom the acute HVPG response to propranolol was assessed, were prospectively included. A targeted metabolomic serum analysis using ultrahigh‐performance liquid chromatography coupled to mass spectrometry was performed. Different combinations of 2‐3 metabolites identifying HVPG responders (HVPG reduction > 10%) were obtained by stepwise logistic regression. The best of these model (AUROC, Akaike criterion) underwent internal cross‐validation and cut‐offs to classify responders/non‐responders was proposed. Results A total of 41/66 (62%) patients were HVPG responders. Three hundred and eighty‐nine metabolites were detected and 177 were finally eligible. Eighteen metabolites were associated to the HVPG response at univariate analysis; at multivariable analysis, a model including a phosphatidylcholine (PC(P‐16:0/22:6)) and a free fatty acid (20:2(n‐6), eicosadienoic acid) performed well for HVPG response, with an AUROC of 0.801 (0.761 at internal validation). The cut‐off 0.629 was the most efficient for overall classification (49/66 patients correctly classified). Two cut‐off values allowed identifying responders (0.688, PPV 84%) and non‐responders (0.384, NPV 82%) with undetermined values for 17/66 patients. Clinical variables did not add to the model. Conclusions The combination of two metabolites helps at identifying HVPG responders to acute propranolol. It could be a useful non‐invasive test to classify the HVPG response to propranolol.

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“…Hepatic fibrosis complicates all chronic liver diseases, whether due to chronic alcoholism, viral B or C infection, or autoimmune, biliary, parasitic or medicinal. It is now accepted that hepatic fibrosis is a dynamic process, causing not only excessive production of matrix components (fibrogenesis) [2], but also a decrease in their degradation (fibrolysis) [3].…”

Section: Introductionmentioning

confidence: 99%

In vivo Antifibrotic Potential of Extracts of Acanthospermum hispidum DC. Evaluated in Wistar Rats Using Diethylnitrosamine

N’do

Hilou

Paré

et al. 2019

IJTDH

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Aims: Liver fibrosis is a chronic disease of the liver. This disease is a stage of passage to liver cancer. The objective of this work was to evaluate the ability of the ethanolic extract of Acanthospermum hispidum to block the progression of hepatic fibrosis induced in rats using diethylenitrosamine (DEN). Study Design: Study of the antifibrotic potential of extracts of Acanthospermum hispidum. Place and Duration of Study: In vivo tests were performed from September 2018 to January 2019. The animal model tests were carried out in the pet shop of the Institute for Health Sciences Jotham et al.; IJTDH, 36(1): 1-9, 2019; Article no.IJTDH.48549 2 Research (IRSS) of Burkina Faso and in the Cytogenetics Laboratory (FSS/ISBA) of the Republic of Benin. Methodology: The evaluation of the antifibrotic activity consisted in treating in wistar rats a liver fibrosis induced with the DEN which is a chemical agent whose effect on the liver has already been confirmed. As a result of the treatment, all animals were removed from the liver and blood. The livers were used for macroscopic and microscopic observations. Blood has been used for the evaluation of biochemical parameters in relation to fibrosis. Results: The analysis of the results of the biochemical parameters in relation to the fibrosis showed that the ethanolic extract of Acanthospermum hispidum at the dose of 250 mg / kg made it possible to obtain an improvement of these parameters compared to the other batches of animals. These results have been confirmed by those of the anatomo-pathological studies. Conclusion: The results of biochemical and histological analyzes revealed a capacity of Acanthospermum hispidum extracts to block the evolution of hepatic fibrosis in the rat. These results confirm the hepatoprotective potential of this medicinal plant used in traditional medicine in Burkina Faso. Original Research Article

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Identification of key metabolic changes during liver fibrosis progression in rats using a urine and serum metabolomics approach

Cited by 80 publications

References 44 publications

Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis

Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis

Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis

In vivo Antifibrotic Potential of Extracts of Acanthospermum hispidum DC. Evaluated in Wistar Rats Using Diethylnitrosamine

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