MC4R and obesity due to melanocortin 4 receptor deficiency: MC4R mutations represent the most prevalent form of monogenic obesity (Farooqi et al., 2003) and both animal models and human patients carrying loss-of-function MC4R mutations exhibit early-onset obesity caused by hyperphagia and reduced energy expenditure (Bolze and Klingenspor, 2009; Kuhnen et al., 2019; Rene et al., 2021).