Here, we provide evidence that hyperinsulinemia triggers fatty liver development and insulin resistance by stimulating hepatic expression of Cd36. A 3w sucrose-enriched diet was sufficient to provoke hyperinsulinemia, increased hepatic Pparγ and Cd36 expression, hepatosteatosis, hepatic insulin resistance, and dysglycemia in CBA/J mice. The gene discussed is PPARG; the disease is Insulin resistance.