Hepatic Metabolomic Analysis in Mice Fed a High Fat Diet with Watermelon and Watermelon Byproducts Shows Improved Lipid Metabolism and Reduction of Chronic Inflammation (P06-023-19)

Abstract

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.