title: Metabolomic analysis of simvastatin and fenofibrate intervention in high-lipid diet-induced hyperlipidemia rats.
abstract: OBJECTIVE
  To investigate the metabolite changes caused by simvastatin or fenofibrate intervention in diet-induced hyperlipidemia rats using a GC-MS-based metabolomic profiling approach.
  
  
  METHODS
  SD rats were fed with high-lipid diet for 4 weeks to induce hyperlipidemia, then the rats were fed with normal diet, and orally administered with simvastatin (10 mg·kg(-1)·d(-1)) or fenofibrate (150 mg·kg(-1)·d(-1)) for 2 weeks. Blood samples were collected once a week, and potential biomarkers were examined using commercial assay kits and a metabolomic approach. The metabolomics data were analyzed using a multivariate statistical technique and a principal component analysis (PCA).
  
  
  RESULTS
  Oral administration of simvastatin or fenofibrate significantly decreased the plasma levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol and increased the plasma level of high-density lipoprotein (HDL) cholesterol in the hyperlipidemia rats. Plasma samples were scattered in the PCA scores plots in response to the diet and to the drugs administered. The main metabolites changed in the hyperlipidemia rats were cholesterol, creatinine, linoleic acid, β-hydroxybutyric acid, tyrosine, isoleucine and ornithine. The plasma level of creatinine was significantly lower in the simvastatin-treated rats than in the fenofibrate-treated rats. The plasma tyrosine concentration was declined following intake of high-lipid diet, which was reversed by fenobrate, but not by simvastatin.
  
  
  CONCLUSIONS
  A series of potential biomarkers including tyrosine, creatinine, linoleic acid, β-hydroxybutyric acid and ornithine have been identified by metabolomic profiling, which may be used to identify the metabolic changes during hyperlipidemia progression.
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Qiu-yu
authors.initials: QY
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Yin-hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Zhen-dong
authors.initials: ZD
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Yao
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Guang-bo
authors.initials: GB
authors.lastname: Cui
authors.affiliation: School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Sun
authors.affiliation: School of Pharmacy, FMHS, The University of Auckland Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Zi-mei
authors.initials: ZM
authors.lastname: Wu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D011345:Fenofibrate / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D007532:Isoleucine / Q000097:blood; D019787:Linoleic Acid / Q000097:blood; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D009952:Ornithine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D014443:Tyrosine / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007532:Isoleucine; D014443:Tyrosine; D002784:Cholesterol; D019787:Linoleic Acid; D019821:Simvastatin; D003404:Creatinine; D009952:Ornithine; D020155:3-Hydroxybutyric Acid; D011345:Fenofibrate