HCRT and obesity due to melanocortin 4 receptor deficiency: Unlike in animal studies, we are unable to distinguish between the contributions of individual differences in orexin signaling that predispose humans to develop obesity, and the consequences of environmental effects of calorie-rich diets and sedentary lifestyles (Kotz et al., 2006; Perez-Leighton et al., 2012, 2013).