Given the rapidly increasing prevalence of combined HF and sugar intake and the large diversity in findings on the role of IL-4 in obesity-associated sequelae, we examined the role of IL-4Rα in a combined HF and high carbohydrate/fructose (HC) diet-induced obesity model (HF + HC)– a model that more closely mimics obesity disease. The gene discussed is IL4; the disease is obesity due to melanocortin 4 receptor deficiency.