Identification of activation of tryptophan–NAD+ pathway as a prominent metabolic response to thermally oxidized oil through metabolomics-guided biochemical analysis

Lei Wang, Dan Yao, Pedro E. Urriola, Andrea R. Hanson, Milena Saqui-Salces, Brian J. Kerr, Gerald C. Shurson, Chi Chen

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Consumption of thermally oxidized oil is associated with metabolic disorders, but oxidized oil-elicited changes in the metabolome are not well defined. In this study, C57BL/6 mice were fed the diets containing either control soybean oil or heated soybean oil (HSO) for 4 weeks. HSO-responsive metabolic events were examined through untargeted metabolomics-guided biochemical analysis. HSO directly contributed to the presence of new HSO-derived metabolites in urine and the decrease of polyunsaturated fatty acid-containing phospholipids in serum and the liver. HSO disrupted redox balance by decreasing hepatic glutathione and ascorbic acid. HSO also activated peroxisome proliferator-activated receptors, leading to the decrease of serum triacylglycerols and the changes of cofactors and products in fatty acid oxidation pathways. Most importantly, multiple metabolic changes, including the decrease of tryptophan in serum; the increase of NAD+ in the liver; the increases of kynurenic acid, nicotinamide and nicotinamide N-oxide in urine; and the decreases of the metabolites from pyridine nucleotide degradation in the liver indicated that HSO activated tryptophan–NAD+ metabolic pathway, which was further confirmed by the upregulation of gene expression in this pathway. Because NAD+ and its metabolites are essential cofactors in many HSO-induced metabolic events, the activation of tryptophan–NAD+ pathway should be considered as a central metabolic response to the exposure of HSO.

Original languageEnglish (US)
Pages (from-to)255-267
Number of pages13
JournalJournal of Nutritional Biochemistry
Volume57
DOIs
StatePublished - Jul 2018

Keywords

  • Mass Spectrometry
  • Metabolomics
  • NAD
  • PPARs
  • Thermally oxidized oil
  • Tryptophan

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