A 1H NMR-Based Metabonomic Investigation of Time-Related Metabolic Trajectories of the Plasma, Urine and Liver Extracts of Hyperlipidemic Hamsters

Abstract

The hamster has been previously found to be a suitable model to study the changes associated with diet-induced hyperlipidemia in humans. Traditionally, studies of hyperlipidemia utilize serum- or plasma-based biochemical assays and histopathological evaluation. However, unbiased metabonomic technologies have the potential to identify novel biomarkers of disease. Thus, to obtain a better understanding of the progression of hyperlipidemia and discover potential biomarkers, we have used a proton nuclear magnetic resonance spectroscopy (1H-NMR)-based metabonomics approach to study the metabolic changes occurring in the plasma, urine and liver extracts of hamsters fed a high-fat/high-cholesterol diet. Samples were collected at different time points during the progression of hyperlipidemia, and individual proton NMR spectra were visually and statistically assessed using two multivariate analyses (MVA): principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Using the commercial software package Chenomx NMR suite, 40 endogenous metabolites in the plasma, 80 in the urine and 60 in the water-soluble fraction of liver extracts were quantified. NMR analysis of all samples showed a time-dependent transition from a physiological to a pathophysiological state during the progression of hyperlipidemia. Analysis of the identified biomarkers of hyperlipidemia suggests that significant perturbations of lipid and amino acid metabolism, as well as inflammation, oxidative stress and changes in gut microbiota metabolites, occurred following cholesterol overloading. The results of this study substantially broaden the metabonomic coverage of hyperlipidemia, enhance our understanding of the mechanism of hyperlipidemia and demonstrate the effectiveness of the NMR-based metabonomics approach to study a complex disease.

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…Thus, hamsters fed with high-fat high-cholesterol diet showed an increase in the urine levels of 3-hydroxybutirate [173]. These results were corroborated at serum level, observing that high fat-fed mice showed an increase in 3-hydroxybutirate concentration [174].…”

Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

“…A total of 35 metabolites in the serum and 36 metabolites in the liver were unambiguously assigned for the 1 H NMR spectra. Assignment of metabolites was made on the basis of comparisons with the published literature (Jiang et al 2013; Liao et al 2007; Zira et al 2013). Their chemical shifts and peak multiplicity are listed in Tables 4 and 5, respectively.…”

Comprehensive Metabolic Profiling of Age-Related Mitochondrial Dysfunction in the High-Fat-Fed ob/ob Mouse Heart

“…Plasma glucose concentrations were measured by 1 H NMR spectroscopy as previously described. 28 Plasma insulin was assayed by standard methods with a two-site microtiter plate-based immunoassay with electrochemical luminescence detection. Ten microliters of whole blood was kept in an ETDA-containing tube for measurement of HbA 1C by an automated high-performance liquid chromatography system (TOSOH G7) targeted from HbA 1C (INSTRU-MED, INC., Atlanta, USA).…”