Transcriptomics and metabolomics reveal tomato consumption alters hepatic xenobiotic metabolism and induces steroidal alkaloid metabolite accumulation in mice

Authors: Dzakovich, Michael; GOGGANS, MALLORY - The Ohio State University; THOMAS-AHNER, JENNIFER - The Ohio State University; MORAN, NANCY - Children'S Nutrition Research Center (CNRC); CLINTON, STEVEN - The Ohio State University; FRANCIS, DAVID - The Ohio State University; COOPERSTONE, JESSICA - The Ohio State University

Submitted to: bioRxiv
Publication Type: Pre-print Publication
Publication Acceptance Date: 4/18/2023
Publication Date: 4/18/2023
Citation: Dzakovich, M.P., Goggans, M.L., Thomas-Ahner, J., Moran, N.E., Clinton, S.K., Francis, D.M., Cooperstone, J.L. 2023. Transcriptomics and metabolomics reveal tomato consumption alters hepatic xenobiotic metabolism and induces steroidal alkaloid metabolite accumulation in mice. bioRxiv. https://doi.org/10.1101/2023.04.18.536606.
DOI: https://doi.org/10.1101/2023.04.18.536606

Interpretive Summary: Tomato consumption is associated with many health benefits including lowered risk for developing certain cancers. It is hypothesized that after absorption, tomato phytochemicals are transported to the liver and alter gene expression in ways that lead to favorable health outcomes. However, the effects of tomato consumption on gene expression and the chemical profile of mammalian liver are not well defined. We hypothesized that tomato consumption would differentially alter mouse liver gene expression and chemical profiles compared to a control diet. C57BL/6 mice were fed a macronutrient matched diet containing either 10% red tomato, 10% tangerine tomato, or no tomato powder for 6 weeks after weaning. Gene expression analyses indicated that tomato type and consumption, in general, altered expression of genes connected to detoxification processes. Chemical profiling experiments revealed clear separation between animals fed tomato supplemented diets compared to animals on control diets. Seventy-five significantly different chemical features (representing 19 different chemical formulas) were identified or tentatively identified as steroidal alkaloids and their metabolites; many of which are reported for the first time in mammals. These data together suggest tomato consumption may impart benefits through their ability to enhance detoxification potential.

Technical Abstract: Tomato consumption is associated with many health benefits including lowered risk for developing certain cancers. It is hypothesized that tomato phytochemicals are transported to the liver and other tissues where they alter gene expression in ways that lead to favorable health outcomes. However, the effects of tomato consumption on mammalian liver gene expression and chemical profile are not well defined. We hypothesized that tomato consumption would alter mouse liver transcriptomes and metabolomes compared to a control diet. C57BL/6 mice (n=11-12/group) were fed a macronutrient matched diet containing either 10% red tomato, 10% tangerine tomato, or no tomato powder for 6 weeks after weaning. RNA-Seq followed by gene set enrichment analyses indicated that tomato type and consumption, in general, altered expression of phase I and II xenobiotic metabolism genes. Untargeted metabolomics experiments revealed distinct clustering between control and tomato fed animals. Nineteen molecular formulas (representing 75 chemical features) were identified or tentatively identified as steroidal alkaloids and isomers of their phase I and II metabolites; many of which are reported for the first time in mammals. These data together suggest tomato consumption may impart benefits partly through enhancing detoxification potential.