Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. Using proteomic approaches, we interrogated hepatocyte protein secretion in two models of murine NASH to reveal striking hepatokine remodelling that is associated with insulin resistance and maladaptive lipid metabolism. We identify arylsulfatase A (ARSA) as a novel hepatokine that is upregulated in NASH and type 2 diabetes. This submission contains proteomic analysis of quadracep lipid rafts with or without overexpression of ARSA.