Beyond the known altered levels of the protective adipokine adiponectin in metabolic diseases, abnormal secretion of hepatokines such as FGF21 and fetuin-A in response to metabolic stress has been shown to disrupt insulin signaling, glucose and lipid metabolism, inflammation, and lipotoxicity, contributing to the development and progression of MASLD. This evidence concerns the gene INS and metabolic dysfunction-associated steatotic liver disease.