We next examined the effect of mutations in zebrafish orthologues of the dominant obesity genes SH2B1, SIM1, BDNF, and MC4R. Compared with larvae free from mutations in sh2b1, larvae with FS/PS mutations in both sh2b1 alleles have lower whole-body levels of LDLc and less vascular lipid deposition (Supp Fig. 13; Fig. 4; Supp Table 11). This evidence concerns the gene SIM1 and obesity due to melanocortin 4 receptor deficiency.