To gain insight into the potential linking pathway between circRNA_002581 and autophagy, we investigated the protein levels of well-documented autophagy regulators and observed that circRNA_002581 knockdown reversed the upregulation of CPEB1 and p-mTOR, the downregulation of PTEN and p-AMPKα both in NASH mice and cell model. This evidence concerns the gene PTEN and metabolic dysfunction-associated steatohepatitis.