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: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/14/2023
Publication Date: 1/11/2024
Citation: Dzakovich, M.P., Goggans, M.L., Thomas-Ahner, J., Moran, N.E., Clinton, S.K., Francis, D.M., Cooperstone, J.L. 2024. Transcriptomics and metabolomics reveal tomato consumption alters hepatic xenobiotic metabolism and induces steroidal alkaloid metabolite accumulation in mice. Molecular Nutrition and Food Research. https://doi.org/10.1002/mnfr.202300239.
DOI: https://doi.org/10.1002/mnfr.202300239

Interpretive Summary: Eating tomatoes has many health benefits, like reducing the risk of certain cancers. After eating tomatoes, compounds released from the diet travel to the liver and change how genes function in ways that lead to better health. However, we don't fully understand how the compounds from tomatoes affect gene expression in the liver. To investigate, we gave mice diets supplemented with two distinct varieties of tomatoes for six weeks and compared them to mice fed similar diets without tomato. We found that mice eating tomato supplemented diets had changes in certain genes related to breaking down chemicals in the liver. Additionally, novel conversion products of tomato steroidal alkaloids not previously reported were found in liver tissue of mice fed tomato enriched diets. Tomato consumption may benefit human health in part by increasing the body's ability to detoxify itself.

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.