Fetal programming of dietary fructose and saturated fat on hepatic quercetin glucuronidation in rats.

Phase II biotransformation of flavonoids generates bioactive metabolites in vivo. However, data on the effect of environmental and physiologic factors and fetal programming on phase II pathways toward flavonoids are limited. We examined the effect of parental exposure to a diet high in saturated fats and fructose 1 mo before conception through lactation on in vitro hepatic uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) activity toward quercetin in parent and offspring rats and the interaction between diet and sex. Parents were fed a diet containing 9.9% coconut fat, 0.5% cholesterol, 30% fructose, and 30% glucose (SFF) or a control (C) diet containing 11% corn oil and 60% glucose. After weaning, offspring were fed the C diet for an additional 12 wk. The glucuronidation rate of microsomal UGT was determined with quercetin 30 μmol/L and 12.5 μg of protein in a total volume of 100 μL after a 15-min incubation at 37°C. Three quercetin glucuronides (7-O-quercetin glucuronide, 4'-O-quercetin glucuronide, and 3'-O-quercetin glucuronide) were quantified. In the parent females, the SFF diet decreased by 29% and 19% the production rate of 3'- and 4'-O-quercetin glucuronide quercetin glucuronides, respectively, compared with the C diet (P ≤ 0.05). The production rate of 7-O-quercetin glucuronide quercetin glucuronide in the female offspring rats born to C dams was 59% larger than in their male counterparts (P < 0.05), but no difference was observed in the offspring of SFF dams. High dietary fructose and saturated fat decreased UGT capacity toward quercetin in female rats and in utero exposure to the diet decreased the glucuronidation capacity of their pups.