Denatonium Benzoate, the Most Bitter Compound, Reduces Weight by Promoting Adipocyte Browning

Objectives: Obesity remains a global health challenge, and promoting white adipose tissue browning has emerged as a promising anti-obesity strategy. This study aimed to investigate the anti-obesity effects of denatonium benzoate (DB) and elucidate its underlying mechanisms. Methods: In order to study the anti-obesity effects of DB and its mechanisms, we used in vivo and in vitro obesity models to study whether DB has anti-obesity effects by participating in fat browning. We investigated the role of DB in high-fat diet (HFD)-induced obese C57BL/6J mice using 36 male animals (8 weeks old, 25 ± 2 g), and evaluated the expression of the adipogenic marker genes Fatty acid-binding protein 4 (Fabp4) and Peroxisome Proliferator-Activated Receptor gamma (PPAR-γ); the thermogenic genes uncoupling protein 1 (Ucp1), Transcription Factor A, Mitochondrial (TFAM), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (Pgc1α), and Adrenergic receptor beta 3 (Adrb3); as well as the adipose browning marker genes Deiodinase, Iodothyronine, Type II (Dio2), PR domain containing 16 (PRDM16), and Peroxisome Proliferator-Activated Receptor alpha (PPAR-α) in 3T3-L1 cells and primary adipocytes with DB treatment. Conclusions: These results indicate that the anti-obesity effects of DB may be related to the browning of white fat, providing a novel potential candidate for anti-obesity drug development.