NAFLD pathogenesis is classically attributed to the “two-hit” hypothesis: First hit – Adipose insulin resistance drives lipolysis and free fatty acid flux, overwhelming hepatic uptake to cause steatosis; Second hit – Prolonged lipid toxicity induces ER stress, mitochondrial damage, and oxidative injury, triggering inflammation and progression to NASH. This evidence concerns the gene INS and metabolic dysfunction-associated steatotic liver disease.