Metabolomic analysis of simvastatin and fenofibrate intervention in high-lipid diet-induced hyperlipidemia rats
Abstract
Qiu-yu XU1, #, Yin-hui LIU1, #, Qi ZHANG1, *, Bo MA1, Zhen-dong YANG1, Lei LIU1, Di YAO1, Guang-bo CUI1, Jing-jing SUN1, Zi-mei WU2
1School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China; 2School of Pharmacy, FMHS, The University of Auckland Private Bag 92019, Auckland 1142, New Zealand
Aim: 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.
Conclusion: 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.
Keywords: simvastatin; fenofibrate; hyperlipidemia; metabolomics; biomarker; creatinine; LDL cholesterol; GC-MS
This study was supported by a grant from the National Natural Science Foundation of China (Grant No 81373478, 81302835) and from the Specialized Research Fund for the Clinical Medicine of Jiangsu Province (Grant No SBL201330086), and from the Jiangsu Province Science Foundation for Youths (No BK20130951).
# These authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail nancyzhang03@hotmail.com
Received 2014-02-24 Accepted 2014-06-23
Keywords:
1School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, China; 2School of Pharmacy, FMHS, The University of Auckland Private Bag 92019, Auckland 1142, New Zealand
Aim: 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.
Conclusion: 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.
Keywords: simvastatin; fenofibrate; hyperlipidemia; metabolomics; biomarker; creatinine; LDL cholesterol; GC-MS
This study was supported by a grant from the National Natural Science Foundation of China (Grant No 81373478, 81302835) and from the Specialized Research Fund for the Clinical Medicine of Jiangsu Province (Grant No SBL201330086), and from the Jiangsu Province Science Foundation for Youths (No BK20130951).
# These authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail nancyzhang03@hotmail.com
Received 2014-02-24 Accepted 2014-06-23