DA-1241, a GPR119 Agonist, Ameliorates Fatty Liver Through the Upregulation of TFEB-Mediated Autophagy

DA-1241 is a novel small-molecule GPR119 agonist. DA-1241 treatment stimulates autophagy induction and transcriptional factor EB (TFEB) nuclear translocation and subsequently reduces hepatic fat accumulation both in vitro and in vivo. DA-1241 treatment increases the lysosomal activity and colocalization of mRFP-LC3 with lipid droplets. The antisteatotic effect of DA-1241 is offset by GPR119 knockdown or in tfeb knockout HeLa cells and liver-specific Tfeb knockout mice.