In a fatty liver, inflammation with activated NF-κB signaling and upregulated cytokines (IL-6, TNFα, and IL-1β) seems to be a pivotal event leading to the development of liver insulin resistance and non-alcoholic fatty liver disease (NAFLD) which both strongly predispose to the development of systemic IR and T2D. This evidence concerns the gene NFKB1 and metabolic dysfunction-associated steatotic liver disease.