Longevity & AgingNatural Flavonoid Acacetin Targets LAMTOR1 to Boost Autophagy and Reverse Fatty Liver
Metabolic dysfunction-associated fatty liver disease (MAFLD) lacks approved treatments. This study shows the natural flavonoid acacetin (ACA) reduces hepatic lipid accumulation and liver injury in a mouse model of steatohepatitis by binding directly to LAMTOR1, a lysosomal membrane protein. This binding disrupts the LAMTOR complex, suppresses MTORC1 signaling, and activates autophagy. The MTORC1-AMPK axis is rebalanced, promoting lipid clearance. Genetic knockdown of LAMTOR1 replicated ACA's beneficial effects, confirming LAMTOR1 as ACA's functional target. These findings reveal a previously uncharacterized therapeutic mechanism and nominate LAMTOR1 as a novel drug target for metabolic liver disease.
