Male C57BL/6J mice fed variations of a high-fat (HF), high-sucrose diet (i.e., 45%–60% kcal from fat) is a well-established diet-induced obesity (DIO) model used to study insulin resistance and other obesity-associated metabolic and inflammation sequelae (i.e., increased tumor necrosis factor (TNF)α and other proinflammatory cytokines, adipose inflammation, insulin resistance) [4,5,6,7]. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.