Thus, TM4SF5-mediated NAFLD-like phenotypes could be triggered following HFD or HFD-DF even for a short period of 1 or 2 weeks via promoted peroxisomal β-oxidation and concomitant mTOR activation and autophagy inhibition, in addition to a TM4SF5-mediated inflammatory environment. Here, TM4SF5 is linked to metabolic dysfunction-associated steatotic liver disease.