INS and obesity due to melanocortin 4 receptor deficiency: While obesity may arise due to a reduction in sympathetic-mediated thermogenesis [11], perhaps due to altered activity in the hypothalamus [12] or reduced beta-adrenergic signalling in the adipose tissue [13,14], on balance, clinical and experimental data also point to weight gain and obesity being associated with region-specific sympathetic nervous activation, with concomitant changes in physiological markers such as blood pressure, insulin resistance, and kidney function.