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

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

RK was rapidly absorbed (T_max ∼15 min), deposited in brain and bioconverted into diverse metabolites in mice. Total bioavailability (AUC_{0-12 h} ) was slightly lower in females than males (566 vs. 675 nmol/mL*min). Total bioavailability in obese mice was almost doubled that of control mice (1197 vs. 679 nmol/mL*min), while peaking times and elimination half-lives were delayed. Higher levels of RK and major metabolites were found in WAT of the obese than normal-weight animals.

RK was highly bioavailable, rapidly metabolized, and exhibited significantly different pharmacokinetic behaviors between obese and control mice. Lipid-rich tissues, especially WAT, could be a direct target of RK. This article is protected by copyright. All rights reserved.