The mechanisms by which IL-1β mediates insulin-resistance have been attributed, at least in part, to downregulation of insulin substrate receptor-1 (IRS-1) (95) and aberrant activity of the transcription factors NF-κB and FOXO1 (Forkhead box protein O1) (106) during obesity or inflammatory conditions. This evidence concerns the gene IRS1 and obesity due to melanocortin 4 receptor deficiency.