High-fat diet-induced obesity alters the dose-dependent metabolism of (–)-epigallocatechin-3-gallate in mice

Obesity is a major risk factor for cardiovascular and liver diseases. Green tea-based dietary supplements have gained popularity for weight management. However, human and animal model studies have reported that high oral bolus doses of (–)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, can cause hepatotoxicity. Obesity can affect the biotransformation enzyme systems, but the effect of obesity on EGCG metabolite profile has not been determined. We hypothesized that pre-existing obesity would cause a shift in the biotransformation of EGCG and enhance the production of oxidative metabolites at higher EGCG doses. To test this hypothesis, we used liquid chromatography-mass spectrometry-based metabolomics to compare the urinary EGCG metabolite profile following administration of vehicle (0.9% sodium chloride) or EGCG (100 or 750 mg/kg) to obese or age-matched lean, male C57BL6/J mice. We found that differences in EGCG metabolism between treatment groups were primarily driven by glucuronidated and oxidation metabolites of EGCG. Significantly higher relative concentrations of cysteinyl EGCG in obese mice compared to lean mice suggest that obesity altered EGCG biotransformation in a manner that may enhance susceptibility to hepatotoxicity. These findings highlight the need for additional research on the mechanisms of EGCG-induced hepatotoxicity across body condition.