Serum Metabolomics Analysis Reveals a Distinct Metabolic Profile of Patients with Primary Biliary Cholangitis

Hao, Juan; Yang, Tao; Zhou, Yang; Gao, Guo-Yuan; Feng, Xing; Peng, Yuan; Yue, Tao; Liu, Chenghai

doi:10.1038/s41598-017-00944-9

Cited by 34 publications

(37 citation statements)

References 34 publications

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“…Glucose set aside, the most noticeable differences were the presence of high citraconate in diabetic individuals, which were not detected in controls. This metabolite is an isomeric carboxylic acid, derived from citrate which is known to inhibit fumarate reduction (Vaidyanathan et al 2001 ; Hao et al 2017 ). As a consequence, this would slow down the rest of the Krebs cycle and therefore limit the use of acetylCoA to produce ATP (You et al 2016 ; Hao et al 2017 ).…”

Section: Resultsmentioning

confidence: 99%

“…This metabolite is an isomeric carboxylic acid, derived from citrate which is known to inhibit fumarate reduction (Vaidyanathan et al 2001 ; Hao et al 2017 ). As a consequence, this would slow down the rest of the Krebs cycle and therefore limit the use of acetylCoA to produce ATP (You et al 2016 ; Hao et al 2017 ). Eventually, excessive acetylCoA may be directed towards de novo lipid synthesis and contribute to lipid accumulation in the liver (Solinas et al 2015 ; Postic and Girard 2008 ).…”

Section: Resultsmentioning

confidence: 99%

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NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice

et al. 2019

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Introduction The rapid expansion of Type 2 Diabetes (T2D), that currently affects 90% of people suffering from diabetes, urges us to develop a better understanding of the metabolic processes involved in the disease process in order to develop better therapies. The most commonly used model for T2D research is the db/db (BKS.Cg-Dock7 < m > +/+ Lepr < db >/J) mouse model. Yet, a systematic 1 H NMR based metabolomics characterisation of most tissues in this animal model has not been published. Here, we provide a systematic organ-specific metabolomics analysis of this widely employed model using NMR spectroscopy. Objectives The aim of this study was to characterise the metabolic modulations associated with T2D in db/db mice in 18 relevant biological matrices. Methods High-resolution 1 H-NMR and 2D-NMR spectroscopy were applied to 18 biological matrices of 12 db/db mice (WT control n = 6, db/db = 6) aged 22 weeks, when diabetes is fully established. Results 61 metabolites associated with T2D were identified. Kidney, spleen, eye and plasma were the biological matrices carrying the largest metabolomics modulations observed in established T2D, based on the total number of metabolites that showed a statistical difference between the diabetic and control group in each tissue (16 in each case) and the strength of the O-PLS DA model for each tissue. Glucose and glutamate were the most commonly associated metabolites found significantly increased in nine biological matrices. Investigated sections where no increase of glucose was associated with T2D include all intestinal segments (i.e. duodenum, jejunum, ileum and colon). Microbial co-metabolites such as acetate and butyrate, used as carbon sources by the host, were identified in excess in the colonic tissues of diabetic individuals. Conclusions The metabolic biomarkers identified using 1 H NMR-based metabolomics will represent a useful resource to explore metabolic pathways involved in T2D in the db/db mouse model. Electronic supplementary material The online version of this article (10.1007/s11306-019-1548-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice

et al. 2019

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“…In receiver operating characteristic (ROC) analysis, an impressive AUC of 0.937 for the training group was reported accompanied by an equally impressive 0.890 for the validation group making metabolomics a feasible diagnostic tool. 34 …”

Section: Biomarkers For Pbc Diagnosismentioning

confidence: 99%

Biomarkers for primary biliary cholangitis: current perspectives

Kouroumalis¹,

Samonakis²,

Voumvouraki³

2018

HMER

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Primary biliary cholangitis (PBC) is a chronic progressive cholestatic disease characterized by destruction of small- and medium-sized intrahepatic bile ducts. It is no longer a rare disease, since many new asymptomatic cases are incidentally identified. Liver biopsy is diagnostically critical but not always feasible or practical to be performed. Many potential, noninvasive, markers have been proposed to replace liver biopsy and further provide the assessment of disease severity and ultimate prognosis. In this review, we evaluated serum biomarkers proposed for diagnosis, extent of fibrosis, disease prognosis and attempts for early prediction of treatment response. Older biochemical and immunological markers are presented along with recent reports including the role of microRNAs and promising results based on proteomics and metabolomics.

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“…Multiple metabolomic studies on HBV+ and HCV+ patients have been reported. For HBV, the studies mostly sought biomarkers of the development of cirrhosis or HCC [ 24 , 46 , 47 , 48 , 49 ] or biomarkers simply of HBV infection itself [ 10 , 28 ]. Similar studies have been reported in the case of HCV for serum biomarkers of progression to HCC [ 21 , 22 , 23 ] and for hepatic fibrosis [ 17 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

et al. 2017

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About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

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Serum Metabolomics Analysis Reveals a Distinct Metabolic Profile of Patients with Primary Biliary Cholangitis

Cited by 34 publications

References 34 publications

NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice

NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice

Biomarkers for primary biliary cholangitis: current perspectives

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

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