The significant influence of SMAPoTN on PI3K-Akt-mTOR signaling observed in the HFD group indicated that the SMAPoTN treatment might not directly affect PI3K signaling, but suppress the development of HCC induced by NASH by improving metabolic pathways, including insulin signaling associated with PI3K-Akt. Here, PIK3CB is linked to metabolic dysfunction-associated steatohepatitis.