We speculate that it may be due to (i) a compensatory down-regulation in adipose tissue to counteract the metabolic stress imposed by obesity; (ii) the decreased production of CILP-2 in adipose tissue may contribute to hepatic IR, similar to adiponectin (Sutinen, et al., 2003); (iii) IR may have a tissue-specific effect on CILP-2 expression (Barnea, et al., 2006). The gene discussed is CILP2; the disease is obesity due to melanocortin 4 receptor deficiency.