A prolonged positive imbalance between energy intake and expenditure resulting inobesity, is associated with chronic inflammation and may be a potential mechanism bywhich obesity leads to insulin resistance (in both humans and mice) [Reviewed in [44], [46], [69].  Expression (level of mRNA) of 3 major pro-inflammatory cytokines,TNF, IL1β and I-L6 was up-regulated in the gastrocnemius muscle of both 24 and40-week-old C57 mice after consumption of the high fat diet (Figure 5A-C). The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.