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). Here, TST is linked to obesity due to melanocortin 4 receptor deficiency.