IRS1 and Obesity: It has been reported that TNF-α is the key mediator of insulin resistance in obesity because it suppresses insulin activity [5] by potently inhibiting the expression and tyrosyl phosphorylation of insulin receptor substrate-1 (IRS-1, the major insulin-like growth factor-I receptor), which might reduce the ability of IRS-1 to transduce signals in the insulin signaling system [6].