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Dynamic Patterns of serum metabolites in fulminant hepatic failure pigs

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Abstract

Fulminant hepatic failure (FHF) is still an intractable disease associated with serious metabolic disorder. Investigating the dynamic changes of serum metabolites during the development of FHF would facilitate revealing the pathogenesis and also promote its treatment. Therefore, this study characterized the dynamic metabonome of serum from FHF Pigs using ultra performance liquid chromatography–mass spectrometry. Based on multiple statistical analysis of the resulting dataset, three types of up-regulated and one type of down-regulated patterns were delineated. Each pattern demonstrated distinct trends at different stages during the whole process of FHF, implying the differential clinical significance of them. Specifically, aromatic amino acids (Pattern 1) and lysophosphatidylcholines (LPCs) (Pattern 4) might be good markers for evaluating the severity of FHF, while some conjugated bile acids, long chain acylcarnitines (Pattern 2) and Glycocholic acid (Pattern 3) could indicate liver injury in the early stage. Inspired from the PCA plot that the pathogenetic condition of FHF aggravated with sampling time, a linear discriminant analysis (LDA) model based on phenylalanine and LPC 18:1 were further constructed for evaluating the severity of FHF. The leave-one-out cross-validation accuracy of 91.67% for the training set and the prediction accuracy of 92.31% for the external validation set confirmed its excellent performance. In conclusion, findings obtained from the present study, including four types of Dynamic Patterns of serum metabolites during FHF development and an LDA model for evaluating the severity of FHF, will be of great help to the research and management of FHF in the future.

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Abbreviations

AAA:

Aromatic amino acids

AASLD:

The American Association for the Study of Liver Diseases

ALT:

Aspartate aminotransferase

BPI:

Base peak intensity

CHO:

Cholesterol

CV:

Coefficient of variation

d-gal:

d-galactosamine

FHF:

Fulminant hepatic failure

GC–MS:

Gas chromatography–mass spectrometry

GCDCA:

Chenodeoxycholic acid glycine conjugate

GUDCA:

Glycoursodeoxycholic acid

HPLC–MS:

High performance liquid chromatography–mass spectrometry

LDA:

Linear discriminant analysis

LOOCV:

Leave-one-out cross-validation

LPCs:

Lysophosphatidylcholines

MELD:

The model for end-stage liver disease

PCA:

Principal components analysis

PLS-DA:

Partial least squares discriminate analysis

PTA:

Prothrombin time activity

QC:

Quality control

TB:

Total bilirubin

TBA:

Total bile acids

UPLC–MS:

Ultra performance liquid chromatography–mass spectrometry

VIP:

Variable importance in the projection

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Acknowledgments

The work was financially supported by National High Technology Research and Development Program of China (863 Program, No. 2011AA020104), National S&T Major Project for Infectious Disease Control of China (No. 2008ZX10002-05), and Science Fund for Creative Research Groups of the National Natural Science Foundation of China (NO. 81121002).

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Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China

    Pengcheng Zhou, Jianzhou Li, Li Shao, Guoliang Lv, Lifu Zhao, Haijun Huang, Anye Zhang, Xiaoping Pan, Wei Liu, Qing Xie, Deying Chen, Yongzheng Guo, Shaorui Hao, Wei Xu & Lanjuan Li

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  1. Pengcheng Zhou
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  2. Jianzhou Li
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  3. Li Shao
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  4. Guoliang Lv
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Correspondence to Lanjuan Li.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 36 kb)

Supplementary material 2 (DOC 28 kb)

MS/MS identification of phenylalanine (TIFF 381 kb)

MS/MS identification of tryptophan (TIFF 450 kb)

MS/MS identification of tyrosine (TIFF 843 kb)

MS/MS identification of GUDCA (TIFF 552 kb)

MS/MS identification of GCDCA (TIFF 554 kb)

MS/MS identification of l-palmitoylcarnitine (TIFF 223 kb)

11306_2011_381_MOESM9_ESM.tif

MS/MS identification of linoleylcarnitine based on its retention time and the characteristic ion fragments (m/z = 85) of long-chain acylcarnitines (TIFF 354 kb)

11306_2011_381_MOESM10_ESM.tif

MS/MS identification of elaidic carnitine based on its retention time and the characteristic ion fragments (m/z = 85) of long-chain acylcarnitines (TIFF 316 kb)

MS/MS identification of glycocholic acid (TIFF 567 kb)

MS/MS identification of LPC 16:0 (TIFF 566 kb)

MS/MS identification of LPC 18:0 (TIFF 509 kb)

11306_2011_381_MOESM14_ESM.tif

MS/MS identification of LPC 18:1 based on its retention time and the characteristic ion fragments (m/z = 184 and m/z = 104) of lysophosphatidylcholines (TIFF 376 kb)

11306_2011_381_MOESM15_ESM.tif

MS/MS identification of LPC 18:2 based on its retention time and the characteristic ion fragments (m/z = 184 and m/z = 104) of lysophosphatidylcholines (TIFF 338 kb)

11306_2011_381_MOESM16_ESM.tif

MS/MS identification of LPC 20:4 based on its retention time and the characteristic ion fragments (m/z = 184 and m/z = 104) of lysophosphatidylcholines (TIFF 401 kb)

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Zhou, P., Li, J., Shao, L. et al. Dynamic Patterns of serum metabolites in fulminant hepatic failure pigs. Metabolomics 8, 869–879 (2012). https://doi.org/10.1007/s11306-011-0381-5

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  • DOI: https://doi.org/10.1007/s11306-011-0381-5

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