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

Authors: WANG, LEI - University Of Minnesota; YAO, DAN - University Of Minnesota; URRIOLA, PEDRO - University Of Minnesota; HANSON, ANDREA - University Of Minnesota; SAQUI, MILENA - University Of Minnesota; Kerr, Brian; SHURSON, GERALD - University Of Minnesota; CHEN, CHI - University Of Minnesota

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/17/2018
Publication Date: 7/1/2018
Citation: Wang, L., Yao, D., Urriola, P., Hanson, A., Saqui, M., Kerr, B.J., Shurson, G., Chen, C. 2018. Identification of activation of tryptophan-NAD+ pathway as a central metabolic response to thermally oxidized oil through metabolomics-guided biochemical analysis. Journal of Nutritional Biochemistry. 57:255-267.

Interpretive Summary: Frying foods uses oils and fats to transfer heat to cook the food as well as to add flavor. At the same time, frying alters oils and fat composition, especially polyunsaturated fatty acid composition and the production of primary and secondary lipid peroxidation products, products which may subsequently affect cell structure and function. The current study evaluated metabolic changes in mice which had been fed heated soybean oil for 4 weeks. Data from this study show that there were systemic changes in the metabolome after feeding heated soybean oil to young mice, most specifically in that there was an activation of genes regulating the metabolism of lipid peroxidation products, including the activation of the tryptophan to NAD pathway which is an essential cofactor in lipid peroxidation product metabolism. This information is important for scientists evaluating the impact of lipid peroxidation products on animal metabolism and on how the metabolic processes in the body can make these compounds less harmful to cell structure and function.

Technical Abstract: Consumption of thermally-oxidized edible oils is associated with adverse health effects, but oxidized oils-elicited metabolic events are not well defined and characterized. In this study, two groups of C57BL/6 mice were fed the diet containing 7% (w/w) control soybean oil diet (CSO) and the diet containing 7% (w/w) heated soybean oil (HSO), respectively, for 4 weeks, and the metabolic responses to HSO were examined through metabolomics-guided biochemical analysis. The results showed that HSO altered serum, urine, and liver metabolomes directly through its metabolites and indirectly through its regulatory effects on antioxidant, lipid, amino acid, nucleotide, and microbial metabolism. The direct contribution of HSO to the metabolomes include the presence of hydroxylalkenoic acid metabolites in urine and the decrease of polyunsaturated fatty acid (PUFA)-containing phospholipids in serum and the liver. HSO disrupted redox balance by decreasing glutathione and ascorbic acid in the liver. HSO also decreased microbial metabolites, including hippuric acid and 4-hydroxyphenylacetic acid in urine, and taurodeoxycholic acid in the liver. The activation of peroxisome proliferator-activated receptor a (PPARa) is an upstream event that may regulate many metabolic responses to the consumption of HSO, including decreases of TAG in serum, decreases of pantothenic acid, acetylcarnitine, and octenoylcarnitine in urine, and increases of suberic acid and azelaic acid in urine. Moreover, the activation of tryptophan-NAD+ pathway was confirmed by the decrease of tryptophan in serum, the increases of NAD+ in the liver, the increases of kynurenic acid, nicotinamide, and nicotinamide N-oxide in urine, and the decrease of pyridine nucleotide degradation in the liver. Because NAD+ and its metabolites are essential cofactors in aldehyde metabolism, fatty acid oxidation, glutathione recycling, and DNA repair, the activation of tryptophan-NAD+ pathway should be considered as is a central metabolic response to the exposure of thermally-oxidized oils.