For example, NAFLD and progression to non-alcoholic steatohepatitis (NASH) are, in part, driven by bacterial products (including unmethylated CpG DNA) entering the liver, ultimately activating intra-hepatic Kupffer cells and CD8+ T cells resulting in inflammation, hepatocyte injury and death, insulin resistance with associated increased hepatic gluconeogenesis, and fibrosis35,36. Here, INS is linked to metabolic dysfunction-associated steatohepatitis.