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

Abstract

Background 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. Objective In the present study, we investigated the impact of consumption of watermelon flesh (WF), rind (WR), and skin (WS) on hepatic gene expression patterns in an obesogenic mouse model. Methods Following a ten-week feeding trial during which C57BL/6 J mice were provided either low-fat (LF) diet, high-fat (HF) diet, or high-fat plus watermelon skin (WS), watermelon rind (WR), or watermelon flesh (WF), hepatic RNA was isolated and RNA sequencing was performed. Bioinformatic approaches were used to determine changes in canonical pathways and gene expression levels for lipid- and xenobiotic-regulating nuclear hormone receptors and other related transcription factors including AhR, CAR, FXR, PPARα, PPARγ, LXR, PXR, and Nrf2. Results There were 9,394 genes that had unchanged expression levels between all 5 diet groups, and 247, 58, and 34 genes uniquely expressed in the WF, WR, and WS groups, respectively. Relative levels of mRNAs regulated by AhR, CAR, and PPARα were upregulated in mice consuming WF compared to HF fed mice, whereas mRNAs regulated mainly by CAR were upregulated in mice consuming WR and WS compared to HF. Conclusions At modest levels of intake reflective of typical human consumption, mice consuming WF, WS, and WR exhibited hepatic gene expression profiles altered from HF. Several of these changes involve genes regulated by ligand-responsive transcription factors implicated in xenobiotic and lipid metabolism, suggesting that modulation of these transcription factors occurred in response to consumption of watermelon skin, rind, and flesh. Some of these changes are likely due to nuclear hormone receptor-mediated changes involved in lipid and xenobiotic metabolism.

Investigating the Efficacy of Saccharomyces boulardii in Metabolic Syndrome Treatment: A Narrative Review of What Is Known So Far

“…Only one study evaluated gene expression following the administration of S. boulardii. Briand, Sulpice [82] reported an increase in the transcription of ABCG5 and ABCG8, as has been reported by other studies on the administration of other bioactive compounds associated with a high-fat diet [113,114]. Wilund, Yu [115] stated that the increase in transcription of ABCG5 and ABCG8 can result in a 50% reduction in cholesterol absorption, which also seems to have occurred in the work of Briand, Sulpice [82], although not in the same proportion.…”

Consumption of Antioxidant-Rich “Cerrado” Cashew Pseudofruit Affects Hepatic Gene Expression in Obese C57BL/6J High Fat-Fed Mice

“…RNA sequencing and analysis was performed as described previously [ 13 ]. To identify genes likely to be direct targets of ligand-activated transcription factors, we evaluated mRNAs known to be regulated by AhR (Aryl hydrocarbon Receptor) [ 14 ], CAR (Constitutive Androstane Receptor) [ 14 ], PPARα (Peroxisome Proliferator Activated Receptor α) [ 14 ], PPARγ (Peroxisome Proliferator Activated Receptor γ) [ 15 ], Nrf2 (Nuclear factor erythroid-2 related factor 2) [ 14 ], PXR (Pregnane X Receptor) [ 14 , 16 ], LXR (Liver X Receptor) [ 17 , 18 ], and FXR (Farnesyl X Receptor) [ 19 ] as described previously by our group [ 13 ]. Due to the multiple compositional differences in the two control diets, we choose in this report not to detail the differences between LF- and HF-fed mice.…”