LEP and obesity due to melanocortin 4 receptor deficiency: Although obesity is associated with hyperleptinemia (Trayhurn 2013; Grosfeld et al. 2002; Palhinha et al. 2019), obese patients frequently develop central and peripheral leptin resistance (Frederich et al. 1995) that limits leptin's ability to be effective in target cells due to reduced ObR expression or disturbed ObR signaling.