Moreover, studies from several laboratories demonstrated that the increased noradrenergic activity at the VMH was demonstrable across a wide variety of animal model systems of the obese, insulin-resistant state, including seasonal insulin resistance, high-fat diet feeding, leptin deficiency, leptin receptor attenuation, lethal yellow (Ay/a) mice with inhibited hypothalamic αMSH, genetic-based insulin resistant, hypertension (SHR rat) and adult offspring of both pregnancy malnutrition and hyperinsulinemia mothers (reviewed in [27]). This evidence concerns the gene LEPR and Insulin resistance.