Metabolomics fingerprinting of liver in the comprehensive evaluation of onion as a functional ingredient in the prevention of metabolic impairments associated to diet-induced hypercholesterolaemia

Abstract

Functional ingredients has been suggested to be a complementary tool for the prevention and management of diseases. Metabolomics is capable of gathering comprehensive data, and appear to best enhance our understanding of the role of food in health and disease. Employment of metabolomics to nutrition research is increasing and applications range from assessing novel biomarkers of dietary intake to intervention studies. The aim was to combine untargeted metabolomics platforms to obtain the liver fingerprint of induced hypercholesterolemia in Wistar rats. The extent to which processed onion may affect the liver regulation and prevent the induced metabolic imbalance was assessed. The liver fingerprint of male Wistar rats (n = 24) fed with three experimental diets: control (C), highcholesterol: 2 % cholesterol and 0.5 % cholic acid (HC), and high-cholesterol enriched with onion (HCO) was obtained with LC-MS, GC-MS and CE-MS analysis, in order to achieve a broad metabolite coverage. Raw data acquired were processed to provide structured data in an appropriate format for data analysis. Reprocessed data were subjected to univariate and multivariate statistical analyses, providing a list of significant metabolites. All results were merged in order to determine the most relevant metabolites that were modified by the onion ingredient. 1169 and 490 features (ESI(+/-) ionization mode, respectively) were obtained after alignment, manual screening and integration correction by LC-MS and 129 features by CE-MS analysis. 75 metabolites were identified with the target metabolite Fiehn RTL library (G1676AA, Agilent), the CEMBIOlibrary and the NIST mass spectra library. In total 618 features in ESI(+) and 369 in ESI(-) LC-MS mode, 67 features in CE-MS and 33 metabolites in GC-MS were found to be statistically significant. Several relevant metabolic changes and related metabolic pathways were found to be impacted by both HC and HCO diet. The model highlighted metabolites, such as e.g., hydroxybutyryl carnitine and palmitoyl carnitine, modified by the HCO diet. These findings could suggest potential impairments in the energy-lipid metabolism, perturbations in the tricarboxylic acid cycle (TCA) cycle and β-oxidation modulated by the onion supplementation in the core of hepatic dysfunction. Processed onion can be considered as a source of multiple bioactive compounds with hepatoprotective properties. Metabolomics shows to be a valuable tool to evaluate the effects of complementary dietetic approaches directed to hepatic damage amelioration or non-alcoholic fatty liver disease (NAFLD) prevention.