Monoterpene phenolic compound thymol promotes browning of 3T3-L1 adipocytes

Purpose Appearance of brown-like adipocytes within white adipose tissue depots (browning) is associated with improved metabolic phenotypes, and thus a wide variety of dietary agents that contribute to browning of white adipocytes are being studied. The aim of this study was to assess the browning effect of thymol, a dietary monoterpene phenolic compound, in 3T3-L1 white adipocytes. Methods Thymol-induced fat browning was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR and immunoblot analysis, respectively. Moreover, the molecular mechanism underlying the fat-browning effect of thymol was investigated by determining expression levels of key players responsible for browning in the presence of kinase inhibitors. Results Thymol promoted mitochondrial biogenesis and enhanced expression of a core set of brown fat-specific markers as well as increased protein levels of PPAR gamma, PPAR delta, pAMPK, pACC, HSL, PLIN, CPT1, ACO, PGC-1 alpha, and UCP1, suggesting its possible role in browning of white adipocytes, augmentation of lipolysis, fat oxidation, and thermogenesis, and reduction of lipogenesis. Increased expression of UCP1 and other brown fat-specific markers by thymol was tightly coordinated with activation of beta 3-AR as well as AMPK, PKA, and p38 MAPK. Conclusion Our findings suggest that 3T3-L1 is a potential cell model for screening browning agents. Thymol plays multiple modulatory roles in the form of inducing the brown-like phenotype as well as enhancing lipid metabolism. Thus, thymol may be explored as a potentially promising food additive for prevention of obesity.