Studies have shown that skeletal muscle in the GK rat is insulin resistant even in the absence of obesity (Goto and Kakizaki, 1981; Steiler et al., 2003), displays preserved mitochondrial function (Lai et al., 2017) and has reduced PPARδ gene expression (Shen et al., 2008) with concomitant hyperglycemia and hyperinsulinemia (Steiler et al., 2003; Kuwabara et al., 2017; Lai et al., 2017), despite normal levels of plasma non-esterified fatty acids (NEFA), and normal skeletal muscle glycogen and IMCL content (Macia et al., 2015). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.