For instance, obesity is regarded as a state of ghrelin resistance, as evidenced by the failure of administered ghrelin to acutely induce food intake in diet-induced obese mice and in obese agouti mice (59–61), the failure of administered ghrelin to reduce energy expenditure in diet-induced obese mice (62), and the attenuated ghrelin-induced GH release in human subjects with obesity (63). Here, GHRL is linked to obesity due to melanocortin 4 receptor deficiency.