We examined insulin signaling mechanisms, pro-ceramide gene expression, and ceramide levels in experimental models of steatohepatitis or hepatic steatosis, including chronic HFD feeding, peripheral (i.p.)nitrosamine exposure (sub-mutagenic doses), and DIO with T2DM and NASH, all of which have histopathologic and biochemical evidence of neurodegeneration, and deficits in learning and memory by Morris water maze testing [104–108]. Here, INS is linked to metabolic dysfunction-associated steatohepatitis.