Many human and animal studies have demonstrated that sOb-R levels are inversely correlated with plasma levels of leptin, BMI, and adiposity (Chan et al., 2002; Lahlou et al., 2000; Laimer et al., 2002; Ogier et al., 2002; Reinehr et al., 2005), suggesting that low levels of the soluble isoform contribute to obesity-related hyperleptinemia and subsequently, leptin resistance. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.