The Putative Caloric Restriction Mimetic Resveratrol has Moderate Impact on Insulin Sensitivity, Body Composition, and the Metabolome in Mice.
SCOPE:Data on resveratrol-(trans-3,5,4'-trihydroxystilbene)-induced caloric-restriction-(CR)-mimicking effects in mice receiving a high-fat diet (HFD) are contradictory. It is hypothesized that this can possibly stem from different bioactivities of resveratrol (RSV) microbial metabolites. METHODS AND RESULTS:C57BL/6Rj mice are fed an ad-libitum HFD supplemented with RSV or its metabolites, dihydroresveratrol (DHR) and lunularin (LUN) (≈28 mg (dihydro)stilbene kg-1 mouse per day). A 40% CR group was included in the study. While CR mice show robust changes in bodyweight and composition, hormone levels and mRNA expression, slight changes are found (more muscle, less adipose tissue) in body composition, leptin, and insulin levels in RSV-supplemented mice compared to ad libitum controls. LUN hardly and DHR does not change the hormone levels measured. Metabolome analysis of serum shows changes in CR mice but only slight, if any, changes in RSV-, DHR-, or LUN-supplemented mice compared to the controls. Evaluating the capability of RSV and its metabolites to inhibit carbohydrate-hydrolyzing enzymes in vitro, it is found that RSV reduced α-glucosidase activity to a stronger extent than DHR and LUN. CONCLUSION:Decelerated carbohydrate breakdown by RSV may have contributed to the moderate impact of dietary RSV on mouse insulin sensitivity (lowered fasting and post-glucose-bolus insulin levels).