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.从没药树脂（Resina Commiphora）中分离得到的天然萜类化合物之一7-氧代卡利特瑞斯酸（7-oxocallitrisic acid，7-OCA）具有脂质代谢调节活性。为揭示其抑制脂肪生成的作用机制，我们基于7-OCA骨架开发了一款光亲和可点击探针，并通过化学蛋白质组学技术筛选其潜在细胞靶点。研究发现，7-OCA可与肉碱棕榈酰转移酶1A（carnitine palmitoyl transferase 1A，CPT1A）直接结合，以增强其活性，从而减少脂质蓄积。本研究阐明了松香酸类化合物调控脂质代谢的作用模式，为以CPT1A为核心靶点的抗肥胖药物研发提供了新的线索。