Background Watermelon intake has demonstrated effects on blood pressure regulation along with other health benefits. Objective We hypothesized that intake of whole watermelon and products made from watermelon rind (WR) and watermelon skin (WS) would remediate metabolic complications in C57BL/6 J male mice fed a diet modeling a Western-style diet. Methods Ten-week-old male C57BL/6 J mice were provided either a low-fat (LF) diet [10% fat (by energy), 8% sucrose (by energy) and no added cholesterol], a high-fat (HF) diet [45% fat (by energy), 20% kcal sucrose (by energy), and 1% (w/w) cholesterol], or an HF diet plus WS, WR, or watermelon flesh (WF) for 10 wk. Dried WF was provided at 8% of total energy (equivalent to 2 servings/d) and watermelon skin and rind were added at 2.25% (w/w, dry weight of additives) of diet. Animals were provided experimental diets ad libitum. Body weights, food intake, and glucose tolerance were determined. Serum insulin, inflammatory markers, microbiome, and the relative hepatic concentrations of 709 biochemicals were measured postmortem. Results The final body weight of the LF control group was significantly lower than that of the HF-fed control group (32.8 ± 0.9 g compared with 43.0 ± 1.7 g, P ≤ 0.05). Mice in treatment groups fed HF supplemented with watermelon products had final body weights similar to those of the HF-fed control mice. Serum insulin concentrations were reduced by ∼40% in mice fed an HF diet with WR supplementation compared with mice fed an HF diet alone (P ≤ 0.05). Depending on the individual species or group, microbiome populations changed significantly. Supplementation with WF resulted in a return to the basal hepatic concentrations of monohydroxy fatty acids and eicosanoids observed in LF-fed mice (P ≤ 0.05). Conclusions In obese male mice, supplementation with each of the watermelon products to an HF diet improved fasting blood glucose, circulating serum insulin concentrations, and changes in hepatic metabolite accumulation. At a modest level of supplementation to an HF diet, fiber-rich additives made from WR and WS further improved glucose metabolism and energy efficiency and shifted the microbiome composition.

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.

Objectives Grapes are nutrient-dense, particularly in polyphenolic compounds. Previous research demonstrates benefits of whole grape and grape skin, seed, and polyphenol intake on glucose homeostasis along with other health benefits. We tested the hypothesis that intake of 4 servings per day of table grape would remediate metabolic complications in C57BL/6 J (C57) male mice fed a high-fat diet with added cholesterol and fructose diet modeling an obesogenic and diabetogenic western-style diet. Methods Groups of mice (n = 12) were provided either low-fat plus placebo diet (LF, 10% kcal fat), high-fat plus placebo (HF, 45% kcal fat), or HF plus grape powder (HF + G), for 8 weeks. Grape powder was provided at ∼10% of total energy of diet. C57 mice were provided experimental diets ad libitum. Body weights, food intake, and glucose tolerance were determined. Postmortem, inflammatory markers, cecal microbiome, and the relative concentrations of hepatic metabolites were determined. Results Fasting blood glucose was reduced in the HF + G group compared to HF-fed mice. The glucose tolerance test demonstrated that the Area Under the Curve (AUC) was also reduced. Further, a significant decrease in circulating levels of insulin were observed with HF + G supplementation. The cecal microbiome from HF + G fed mice overlapped with both the HF and LF controls, but also had characteristic shifts that were unique to grape powder consumption. Metabolomic analysis indicated grape consumption impacted inflammation and β-oxidation biomarkers indicating some remediation of hepatic pathologies associated with HF food consumption. The most significantly different hepatic metabolites included grape-derived S-methymethionine and trigonelline, while other murine hepatic metabolites significantly regulated by diet included myo-inositol and 15-HETE. Conclusions Table grape supplementation with a HF western-style diet significantly improved fasting blood glucose, circulating insulin concentrations, and HOMA-IR in C576J/Bl male mice. demonstrating an anti-diabetic effect of grape powder. At modest level of supplementation equivalent to 4 servings/day, grape powder also improved microbiome composition and changed relative levels of specific hepatic metabolites. Up-regulation of 15-HETE by diet suggests grape powder consumption may enhance PPARγ-directed gene expression, consistent with increases in glucose sensitivity observed in this study. Funding Sources California Table Grape Commission.

Objectives Watermelon is a nutrient-dense fruit shown previously to produce health benefits, particularly regarding blood pressure regulation. We tested the hypothesis that intake of whole watermelon flesh and value-added watermelon components would improve metabolic conditions in C57BL/6 J male mice fed a high-fat, high-sucrose diet modeling an obesogenic Western diet (HF). We further hypothesize that metabolomic profiling will show changes in relative levels of compounds related to lipid and glucose metabolism, and chronic inflammation. Methods In a prior study (Becraft et al., 2018), groups of mice (n = 8) were provided either low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 45% kcal fat), HF plus Watermelon Skin (HF + WS), HF plus Watermelon Rind (HF + WR), or HF plus Watermelon Flesh (HF + WF) for 10 weeks. Watermelon flesh was provided at 10% of total energy and skin and rind were added at ∼ 0.2% (w/w) of diet. After ten weeks, animals were euthanized, and liver tissue saved for metabolomic analysis. Liver tissue samples were homogenized, and an identical mass equivalent of liver was subjected to methanol extraction and split into aliquots for analysis by ultrahigh performance liquid chromatography/mass spectrometry in the positive, negative or polar ion mode. There were 709 biochemicals identified and analyzed between groups. Welch's 2-sample t-test was performed with ArrayStudio (Omicsoft) or R software on log transformed data to compare data between experimental groups. Estimate of the false discovery rate (Q value) was calculated and Q ;< 0.05 used as an indication of high confidence in a result. Results Principal component analysis showed segregation of groups along three different components, representing 24.8%, 19.4%, and 9.0% of the variation. Profound differences were found in LF vs. HF liver tissue. Compared to HF-fed mice, mice fed WF showed reduced levels of bile acids and pro-inflammatory compounds 12-HETE, 15, HETE, and PGF2 (all P < 0.05) in the liver. Conclusions In mice consuming a high-fat western style diet, regular intake of watermelon flesh, and fiber-rich products made from rind and skin all improved metabolism as evidenced by metabolomic analysis of liver tissue. Most notably were reductions in pro-inflammatory compounds including HETEs and Prostaglandin F2. Funding Sources National Watermelon Promotion Board.