Dehydrozingerone reprograms adipocyte metabolism by coordinating thermogenesis and lipogenesis
Browning is a process wherein white adipocytes differentiate into brown-like adipocytes. This process is one of the key signatures of overcoming obesity. Notably, several functional foods and dietary supplements can induce browning in human body. One such naturally occurring compound is dehydrozingerone (DHZ), which is known for its beneficial effects, including antioxidant properties. In this study, DHZ was evaluated for its effect on fat reduction in 3T3-L1 cells prior its consideration as a potential anti-obesity therapeutic. The results underpin that DHZ acts as a key activator of browning, as shown by increased expression of brown adipose tissue (BAT) markers such as uncoupling protein 1 (UCP1), PR/SET domain 16 (PRDM16), cell death-inducing DFFA-like effector A (CIDEA), T-box transcription factor 1 (TBX1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) . These changes in gene expression may be associated with activation of the AMP-activated protein kinase (AMPK) pathway, and potentially mediated by the browning effect of DHZ on 3T3-L1 adipocytes. Furthermore, the treatment of DHZ also increased expression of Carnitine palmitoyltransferase 1 (CPT1), acyl-CoA synthetase long-chain family member (ACSL), and Sirtuin 1 (SIRT1), suggesting enhanced fatty acid oxidation. While the expression of Srebp1 and LpI was reduced. These findings suggest that DHZ may possibly enhances thermogenesis and promote browning in white adipocytes, thereby suppressing lipogenesis. In conclusion, DHZ showed dual effects lipid metabolism, contributing to development of a brown-like phenotype. The results depict that DHZ could serve as a promising therapeutic candidate for the management of obesity. In addition, molecular docking analysis demonstrated strong binding affinity between DHZ and the target protein, further supporting its potential as a novel therapeutic agent. However, these considerations are preliminary, and further studies, including diet-induced animal model, are required to elucidate its mechanism of action.