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.