Changes in the metabolic profile of rat liver after α-tocopherol deficiency as revealed by metabolomics analysis

Metabolomics is an approach in which the profiles of metabolites in different tissues and/or biofluids are investigated to understand the changes induced following a modulation. We used this approach to investigate the biochemical effects of a-tocopherol in the liver using a rat model. Rats (21-day-old) were fed either an a-tocopherol-sufficient control (n = 10) or an a-tocopherol-deficient (n 10) diet for 2 months before sacrifice. Livers were homogenized in methanol-chloroform-water (3 : 1 : 1, v/v/v), and the polar phase extracts of the liver samples were analyzed using H-1 NMR. Multivariate statistical analysis of the data was performed using principal component analysis and orthogonal partial least squares-discriminant analysis. Identification of H-1 NMR signals was performed primarily using the Human Metabolome Database, Biological Magnetic Resonance Data Bank and previous literature, and confirmed by spiking with metabolites and applying two-dimensional NMR. The statistical analysis revealed that alpha-tocopherol deficiency caused an increase in carnitine, choline, L-valine, L-lysine, tyrosine and inosine content and a reduction in glucose and uridine 5'-monophosphate content. Changes in carnitine and glucose suggest a possible shift in energy metabolism. Copyright (C) 2010 John Wiley & Sons, Ltd.