IRS1 and obesity due to melanocortin 4 receptor deficiency: As individuals with heritable predisposition to diabetes, LBW humans, LP offspring rats and mice exposed to maternal obesity during gestation and lactation had similar impairments in insulin signalling proteins in WAT (with IRS1 downregulation in mice also shown to be regulated in a cell-autonomous manner), common pathways may be initiated in response to a range of suboptimal early conditions that may drive the development of peripheral insulin resistance [2, 5, 8, 28].