Neil F. Shay, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Watermelon intake has been shown to produce a slight hypotensive effect and may favorably impact metabolism in other ways. Previously, we demonstrated that intake of watermelon impacted gene pathways related to lipid metabolism, inflammation, vasoconstriction, among others (Egea et al., 2020). The objective in this study was to compare the intake of watermelon and watermelon byproducts to consumption of two amino acids abundant in watermelon, arginine and citrulline, as well as lycopene and s-methylmethionine. Gene expression profiling was used to compare different treatments, in both male mice fed high fat diets with the various supplements, and a cell culture line, HepaRG.
Methods: Male mice (n=8-12 per group) were fed low-fat and high-fat (HF) control diets or HF diet supplemented with freeze dried watermelon flesh or the purified compounds, arginine, citrulline, lycopene, or s-methylmethionine (~ 1%, w/w). In a second study, the HepaRG cell line was used. In addition to being exposed to normal concentrations of amino acids in the cell culture media, treatment groups were also exposed to supplemented levels of arginine, citrulline, and lycopene.
I both trials, cellular RNA was isolated and used for RNA Sequencing (RNASeq). Gene expression patterns and most up- and down-regulated genes were used to compare the various groups to each other.
Results: Part 1: Intake of watermelon flesh and arginine impacted expression of cyp450 genes similarly; Cyp2c9 was profoundly upregulated by these two treatments. Additionally, arginosuccinate lyase was downregulated in mice consuming supplemental levels of citrulline and s-methylmethionine. Upset plot analysis demonstrated that citrulline and s-methylmethionine shared 43 genes significantly down-regulated.
Part 2: Cells exposed to elevated levels of arginine, citrulline, and lycopene produced both up- and down-regulated genes. Exposure to arginine and citrulline produced several common gene pathways to be significantly regulated, including immune system and cell degranulation.
Conclusions: In male mice, supplementation of HF diets with arginine or citrulline most resembled changes in gene expression associated with watermelon intake. In HepaRG cells, arginine and citrulline produced a more similar effect in gene expression vs. the effect of lycopene.
Funding Sources: National Watermelon Promotion Board
