title: A proton nuclear magnetic resonance metabonomics approach for biomarker discovery in nonalcoholic fatty liver disease.
abstract: This study was undertaken to discover novel biomarkers for the noninvasive early diagnosis of nonalcoholic fatty liver disease (NAFLD). A methionine and choline deficient (MCD) diet was used to represent different stages of NAFLD in male C57BL/6 mice. (1)H NMR spectroscopy and principal components analysis (PCA) were used to investigate the time-related biochemical changes in mice sera induced by the MCD diet. Many serum metabolites' concentrations changed between control and MCD-fed mice. Hierarchical cluster analysis (HCA) and artificial neural networks (ANNs) were used to select the least number of metabolites to be used for the noninvasive diagnosis of various stages of NAFLD; four potential biomarkers, serum glucose, lactate, glutamate/glutamine, and taurine were selected. To verify the diagnostic accuracy of these selected metabolites, their serum concentrations were measured in healthy controls (n = 28), NAFLD patients with steatosis (n = 15), steatosis patients with necro-inflammatory disease (n = 11), and NASH patients (n = 6). On the basis of results from MCD-fed mice model, clinical tests, and previous reports, we propose using the levels of the four metabolites for diagnosing NAFLD at various stages. Furthermore, the probability of developing NAFLD at a particular stage was assessed by multinomial logistic regression (MLR) based on the clinical results of the four serum metabolites.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Yan
authors.forename: Qijun
authors.initials: Q
authors.lastname: Liu
authors.forename: Chaohui
authors.initials: C
authors.lastname: Yu
authors.forename: Handong
authors.initials: H
authors.lastname: Wei
authors.forename: Youming
authors.initials: Y
authors.lastname: Li
authors.forename: Xuemin
authors.initials: X
authors.lastname: Zhang
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000737:chemistry; D004032:Diet; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D018698:Glutamic Acid / Q000097:blood; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D016015:Logistic Models; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D025341:Principal Component Analysis; D013654:Taurine / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D013654:Taurine; D019344:Lactic Acid; D018698:Glutamic Acid