Additionally, Mc4r−/− mice that have not yet attained full obesity, exhibit reduced locomotor activity (Chen et al., 2000; Ste Marie et al., 2000; Butler et al., 2001) that is accompanied by a higher respiratory exchange ratio (Dean et al., 2009; Speakman, 2013). Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.