NMR-based metabolomics reveals tissue metabolic responses to tetramethoxy gossypol in cottonseed oil

BACKGROUND Cottonseed oil is one of the most widely consumed cooking oils because of its high nutritional benefits and relatively low price. The present study evaluated the effects of tetramethoxy gossypol (TMG), a rarely reported degradation product of free gossypol produced in crudely extracted cottonseed oil, on the metabolic responses of liver, heart, spleen, kidney and lung tissues in rats using proton nuclear magnetic resonance (H-1 NMR) spectroscopy combined with chemometric and bioinformatics techniques. RESULTS Endogenous low-molecular-weight metabolites in rat liver, heart, spleen, kidney and lung tissues were profiled by H-1 NMR spectroscopy. The unsupervised principal components analysis and the supervised orthogonal partial least squares discriminant analysis revealed that the metabolic profiles in liver samples were greatly changed after TMG administration. Twenty significantly changed liver metabolites were screened out and further evaluated by receiver operating characteristic curve analysis, which were closely related to amino acid, glutathione, energy and lipid metabolism. CONCLUSION Concerning the potential chronic exposure to TMG in cottonseed oil and other cottonseed products, the cumulative effects of dietary TMG on tissues, especially the liver, should be noted when improving the quality control standard of cottonseed oil. (c) 2022 Society of Chemical Industry.