LEP and obesity due to melanocortin 4 receptor deficiency: Horvat et al. (2000) identified four major quantitative trait loci (QTL) responsible for their divergent phenotype, which is independent of known mutations in the leptin system or individual obesity-associated gene loci such as Cpe and Ay. Subsequent studies led to the identification of the Deptor gene as a novel regulator of adipogenesis (Laplante et al. 2012) and mitochondrial thiosulfate sulfurtransferase (Tst) as the causative gene for resistance to obesity (Morton et al. 2016).