We wish to highlight areas of advancement made possible by this model including; emerging appreciation of the “thrifty gene” hypothesis in the context of obesity, the concept of how chronic inflammation may drive obesogenesis, the impact of acute forms of inflammation to the brain and periphery during chronic obesity, the role of dysfunctional insulin metabolism on lipid metabolism and vascular damage, the mechanistic basis for altered vascular function as well as novel parallels between the human condition and the female JCR:LA-cp rat as a model for polycystic ovary disease (PCOS). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.