A provocative conclusion emerging from our study and other ‘negative’ studies is that obesity-induced insulin resistance in muscle, the primary organ accounting for insulin-mediated glucose disposal, is not dependent on inflammatory signalling in muscle itself; this in turn can be extrapolated to suggest that development of insulin resistance in muscle during obesity does not require inflammatory mediators that affect skeletal muscle. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.