IRS1 and metabolic dysfunction-associated steatotic liver disease: Mechanistically, TRAF3 regulates TAK1 autophosphorylation through a K63-linked ubiquitination chain, which enhances the activation of the downstream IKKβ-NF-κB and MKK-JNK-IRS1 signaling cascades, and simultaneously disrupts the AKT-GSK3β/FOXO1 signaling, exacerbating NAFLD insulin resistance and thus promoting hepatic steatosis and inflammatory responses (33).