To identify the specific cell types mediating these effects, we deleted the miR-7 family in neurons expressing the Leptin receptor (Lepr), Pomc, Agrp and Sim1. We found that Sim1-cre;mir-7fl/fl mice exhibited severe obesity due to increased food intake and decreased energy expenditure, associated with increased linear growth and increased insulin secretion. Here, SIM1 is linked to obesity due to melanocortin 4 receptor deficiency.