IRS1 and steatosis: The increased expression (Fig. 5a and b) and activity (Fig. 5c) of CYP4A and the ROS generation (Fig. 5d) in steatosis spheroids were distinctly decreased by HET0016 treatment, which contributed to a decrease in ER stress signaling, such as PERK, IRE1, ATF6, and p-JNK, and partially recovered insulin signaling, such as p-insulin receptor substrate 1 (p-IRS) and p-AKT (Fig. 5e).