AKT1 and obesity due to melanocortin 4 receptor deficiency: Analysis of InsrIgf1rAkt pathway activity in SI crypt lysates showed increased phosphorylation of InsrIgf1r and Akt as well as upregulation of several genes associated with PI3K and Akt signalling, which is in line with pronounced hyperinsulinaemia and confirms previous findings that Igf1insulin signalling induces hyperproliferation in diet-induced obesity (Extended Data Figs. 1r–u and 9a–c).