Differential Effects of Grape Powder and Its Extract on Glucose Tolerance and Chronic Inflammation in High-Fat-Fed Obese Mice

The objective of this study was to determine the anti-inflammatory properties of grape powder (GP) or GP extract (GE) and examine (1) which polyphenol metabolites in GE were bioavailable, (2) the impact of GP and GE on glucose tolerance and inflammation in obese mice, and (3) if bioavailable polyphenols in GE decrease markers of inflammation in primary adipocytes. In experiment 1, C57BL/6J mice were gavaged with GE and serum polyphenols were measured. In experiment 2, mice were fed high-fat diets supplemented with 3% GP or 0.02% GE for 18 weeks and markers of inflammation were measured. In experiment 3, human adipocytes were treated with the bioavailable polyphenols quercetin 3-O-glucoside (Q3G) or quercetin 3-O-glucuronide (Q3GN) and markers of inflammation were measured. Serum Q3G and Q3GN increased at 1 h post-GE gavage and decreased thereafter. GP supplementation improved glucose tolerance at 5 weeks and decreased markers of inflammation similar to 20-50% in serum and adipose tissue at 18 weeks. Q3G, but not Q3GN, attenuated TNF alpha-mediated inflammatory gene expression similar to 30-40% in human adipocytes, possibly by suppressing c-Jun-NH2 terminal kinase and c-Jun activation. In summary, (1) Q3G and Q3GN are bioavailable polyphenols in GE, (2) GP acutely improves glucose tolerance and chronically reduces markers of inflammation in obese mice, and (3) Q3G reduces several markers of inflammation in human adipocytes.