GHRL and obesity due to melanocortin 4 receptor deficiency: In a study by Marzullo et al., the obese subjects with low resting energy expenditure (impaired energy balance) exhibited lower active ghrelin levels, compared with obese subjects with high energy expenditure, indicating that ghrelin secretion and activity might be decreased in cases of obesity with impaired energy expenditure, as part of an obesity-related compensatory mechanism [20].