Glucose Metabolism and Cecal Microbiome Populations Are Improved and Hepatic Biochemical Levels Altered with Consumption of Grape Powder by High-fat Fed C57BL/6 J Mice (P06-024-19)

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. 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. 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. 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. California Table Grape Commission.