Nuclear Magnetic Resonance-Based Blood Metabolic Profiles of Rats Exposed to Short-Term Caloric Restriction

Caloric restriction increases the life-span of a number of organisms. The relationship between the increase in life-span and the extent of caloric restriction, however, varies among species. The underlying mechanisms are yet unknown, but appear to be related to changes in metabolism. In order to investigate the metabolic response of caloric restriction of rats, here is presented the first nuclear magnetic resonance (NMR) spectroscopy-based study of how blood metabolite profiles are influenced by graded levels of caloric restriction. The study involved three groups of obese rats exposed to 0, 20, and 40 percent caloric restriction for five days. Blood serum from each individual was analyzed by H-1 NMR and the resulting spectra were subjected to multivariate analysis by unsupervised principal component analysis and supervised orthogonal-partial least square discriminant analysis. The analyses revealed that a response to caloric restriction was present at 20 percent caloric restriction. The metabolites that distinguished the profiles at 20 percent restriction deviated from those at 40 percent restriction. The changes induced by caloric restriction were most clearly observed as an increased level of 3-hydroxybutyrate, and decreased levels of lipids and pyruvate. The metabolic responses of rats exposed to caloric restriction are in good agreement with a switch in metabolism from anabolic pathways towards fatty acid catabolism and gluconeogenesis, which is consistent with previous observations for mice.