IGFBP3 and obesity due to melanocortin 4 receptor deficiency: Top downregulated genes included those previously associated with diabetes and obesity, such as Manf [66] and Creld2 [34] that facilitate protein folding (Fig. 5C), and Igfbp3 and Igfbp7, two structurally similar proteins that regulate the bioavailability of IGFs and insulin.