Photoaffinity-Based Chemical Proteomics Reveals 7-Oxocallitrisic Acid Targets CPT1A to Trigger Lipogenesis Inhibition

One of the natural terpenoids isolated from Resina Commiphora, 7-oxocallitrisic acid (7-OCA), has lipid metabolism regulatory activity. To uncover its lipogenesis inhibition mechanism, we developed a photoaffinity and clickable probe based on the 7-OCA scaffold and performed chemical proteomics to profile its potential cellular targets. It was found that 7-OCA could directly interact with carnitine palmitoyl transferase 1A (CPT1A) to promote its activity to reduce lipid accumulation. The present work reveals our understanding of the mode of lipid mebabolism regulation by abietic acids and provides new clues for antiobesity drug development with CPT1A as a main target.