Intake of Watermelon and Watermelon Byproducts in Male Mice Fed a Western-Style Obesogenic Diet Alters Hepatic Gene Expression Patterns, as Determined by RNA Sequencing

Consumption of watermelon has been associated with beneficial effects on metabolism, including reductions in systolic blood pressure, improved fasting blood glucose levels, and changes in hepatic metabolite accumulation. Objectives: In the present study, we investigated the impact of consumption of watermelon flesh (WF), watermelon rind (WR), and watermelon skin (WS) on hepatic gene expression patterns in an obesogenic mouse model.

At modest levels of intake reflective of typical human consumption, mice in the WF, WS, and WR groups exhibited hepatic gene expression profiles that were altered when compared to mice in the HF control group. Several of these changes involve genes regulated by ligand-responsive transcription factors implicated in xenobiotic and lipid metabolisms, suggesting that the modulation of these transcription factors occurred in response to the consumption of WS, WR, and WF. Some of these changes are likely due to nuclear hormone receptor-mediated changes involved in lipid and xenobiotic metabolisms.

Hepatic RNA was isolated and RNA sequencing was performed following a 10-week feeding trial during which C57BL/6 J mice were provided either a low-fat diet (LF), high-fat diet (HF; controls), or HF plus either WS, WR, or WF. Bioinformatic approaches were used to determine changes in the canonical pathways and gene expression levels for lipid- and xenobiotic-regulating nuclear hormone receptors and other related transcription factors, including the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), farnesyl X receptor, peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma, liver X receptor, pregnane X receptor, and nuclear factor erythroid 2-related factor 2.

There were 9394 genes that had unchanged expression levels between all 5 diet groups, and 247, 58, and 34 genes were uniquely expressed in the WF, WR, and WS groups, respectively. The relative levels of mRNAs regulated by AhR, CAR, and PPARα were upregulated in mice in the WF group, as compared to the HF control mice; in comparison, mRNAs regulated mainly by CAR were upregulated in mice in the WR and WS groups, compared to those in the HF control group. Conclusions: At modest levels of intake reflective of typical human consumption, mice in the WF, WS, and WR groups exhibited hepatic gene expression profiles that were altered when compared to mice in the HF control group. Several of these changes involve genes regulated by ligand-responsive transcription factors implicated in xenobiotic and lipid metabolisms, suggesting that the modulation of these transcription factors occurred in response to the consumption of WS, WR, and WF. Some of these changes are likely due to nuclear hormone receptor-mediated changes involved in lipid and xenobiotic metabolisms.