Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry

A novel metabonomic method based on fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC/MS-IT-TOF) was applied to study the metabolic changes of plasma and urine in depression and excess fatigue rats. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied for classifying the depression, excess fatigue and the control rats. Metabolites which were important for the classification in the three groups of rats were selected as potential biomarkers and identified by MSn information achieved from UFLC/MS-IT-TOF analysis. Spermine, propionylcarnitine, butyrylcarnitine, phenylalanine, lysophosphatidylcholine (LPC) C14:0 and LPC C18:2 were down-regulated, methyl-hippuric acid and chenodeoxycholic acid (CDCA) were up-regulated significantly in plasma of the excess fatigue rats. Spermine, leucine, propionylcarnitine, and butyrylcarnitine decreased, hippuric acid, methyl-hippuric acid, cholic acid, CDCA and LPC C16:0 increased markedly in plasma of the depression rats. Ethyl N2-acetyl-L-argininate and N-methyl-2-pyridone-5-carboxamide (2-PY) (or N-methyl-4-pyridone-3-carboxamide (4-PY)) were down-regulated, leucylproline and pantothenic acid were up-regulated remarkably both in urine of depression and excess fatigue rats. The concentration of kynurenic acid and N2-succinyl-L-ornithine was low in urine of depression rats compared with control rats. Based on the data, correlation networks for depression and excess fatigue rats revealed the abnormality of nicotinate and nicotinamide metabolism, arginine metabolism, cholesterol metabolism, tryptophan metabolism and kynurenine metabolism in depression rats, and in excess fatigue rat alterations of energy metabolism, nicotinate and nicotinamide metabolism and lecithin metabolism. Our results provide novel insights in the complex metabolic mechanisms occurring in depression and excess fatigue rats.