Wild type and ob/ob mice showed that leptin's increment administration increased atherosclerosis and heart disease risk, independent of BMI, serum concentrations of lipid, and insulin sensitivity [36]. On the other hand, ob/ob deficient, leptin receptor-deficient, and apolipoprotein E (ApoE) mice demonstrated leptin's lack of protection against atherosclerosis [15,36]. This evidence concerns the gene INS and atherosclerosis.