An elegant study in wild-type mice demonstrated that chronic stress combined with a high-fat diet results in insulin derepression of NPY neurons in the central amygdala, thereby causing exaggerated obesity and hyperinsulinemia.352 Specifically, mice subjected to chronic stress combined with a high-fat diet developed aggravated obesity due to an increase in caloric intake and a reduction in energy expenditure. Here, NPY is linked to obesity due to melanocortin 4 receptor deficiency.