In particular, methionine adenosyltransferases I/III (encoded by MAT1A), the key enzymes involved in methionine metabolism, and ASMase-induced ceramide generation engage in a reciprocal inhibitory process in which increased ceramide levels generated by ASMase repress MAT1A expression, leading to increased ASMase expression, causing a self-sustained vicious cycle of relevance to ASH/NASH development [100,101]. This evidence concerns the gene SMPD1 and metabolic dysfunction-associated steatohepatitis.