LEP and obesity due to melanocortin 4 receptor deficiency: Because key leptin signaling events take place in restricted cell types in the hypothalamus, it has been difficult to resolve the role of this or other molecules in clinical “leptin resistance.” Pharmacologic SOCS3 inhibitors capable of enhancing leptin action have not been developed, and genetic evidence that SOCS3 or other molecules cause leptin resistance in human obesity has also not been reported.