Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro

Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro. High-fat diet (HFD)-induced obesemice and genetically obese db/dbmice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor g (PPARγ) and CCAAT/enhancerbinding protein a (C/EBPα), were reduced while the key factor of energymetabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice. Furthermore, VAinhibited lipid accumulation and reduced hepatotoxic/inflammatory markers in liver tissues of mice and HepG2 hepatocytes. VA treatment also decreased differentiation of 3T3-L1 adipocytes by regulating adipogenic factors including PPARγ and C/EBPα. AMPKα small interferingRNAwas used to examinewhether AMPK was associatedwith the actions of VA. InAMPKα-nulled 3T3- L1 cells, the inhibitory action ofVAon PPARγ andC/EBPα was attenuated. Furthermore, in brown adipose tissues of mice and primary cultured brown adipocytes, VAincreasedmitochondria- and thermogenesis-related factors such as uncoupling protein 1 and PPARγ-coactivator 1-a. Taken together, our results suggest that VA has potential as an AMPKα- andthermogenesis-activatingantiobesity agent.