We demonstrate that IL-1RI−/− mice maintained on HFD for 6 mo develop glucose intolerance and insulin resistance coupled with a switch in adipose morphology from hyperplasia after 3 mo HFD to hypertrophy after 6 mo HFD, augmentation of adipose inflammation, loss of adipose insulin sensitivity, hepatosteatosis, and hepatic IR. The gene discussed is INS; the disease is Insulin resistance.