Influence of Diet-Induced Obesity on the Bioavailability and Metabolism of Raspberry Ketone (4-(4-Hydroxyphenyl)-2-Butanone) in Mice.

OBJECTIVES

Raspberry ketone (RK) is the primary aroma compound in red raspberries and a dietary supplement for weight loss. This work aims to 1) compare RK bioavailability in male versus female, normal-weight versus obese mice; 2) characterize RK metabolic pathways.

METHODS

Study 1: C57BL/6J male and female mice fed a low-fat diet (LFD; 10% fat) receive a single oral gavage dose of RK (200 mg kg ). Blood, brain, and white adipose tissue (WAT) are collected over 12 h. Study 2: Male mice are fed a LFD or high-fat diet (45% fat) for 8 weeks before RK dosing. Samples collected are analyzed by UPLC-MS/MS for RK and its metabolites.

RESULTS

RK is rapidly absorbed (T  ≈ 15 min), and bioconverted into diverse metabolites in mice. Total bioavailability (AUC ) is slightly lower in females than males (566 vs 675 nmol mL min ). Total bioavailability in obese mice is almost doubled that of control mice (1197 vs 679 nmol mL min ), while peaking times and elimination half-lives are delayed. Higher levels of RK and major metabolites are found in WAT of the obese than normal-weight animals.

CONCLUSIONS

RK is highly bioavailable, rapidly metabolized, and exhibits significantly different pharmacokinetic behaviors between obese and control mice. Lipid-rich tissues, especially WAT, can be a direct target of RK.