In obese humans, a shortage of circulating Orexin-A levels and a diminished response of its receptors in fatty tissues have been noted, but due to the lack of studies, we are not yet able to understand the different influence of individual responses to Orexin-A environmental factors such as a high-calorie diet and a sedentary lifestyle in the development of obesity, but we certainly know that physical activity is able to improve the clinical results in the treatment of this condition even in old age (Hao et al., 2017). Here, HCRT is linked to obesity due to melanocortin 4 receptor deficiency.