How can this hypothesis be addressed in human subjects? A number of clinical trials have already been initiated with the intention of improving insulin resistance by attenuating inflammation. Many of these have focused on the blockade of single cytokines or their receptors such as TNFa, IL1 and MCP1 (CCR2 antagonist). While the record on these trials is mixed, the complexity of inflammatory pathways elicited during obesity suggests that inhibition of only a single cytokine is not likely to be sufficient. Additionally, because numerous studies have implicated the NFkB pathway in obesity-induced inflammation, NFkB inhibitors have been contemplated. Salsalate was originally resuscitated due to its perceived activity to block NFkB and hence to block inflammation. However, although clinical studies on this drug have been promising, precisely how salsalate works, what its target is, and whether it actually functions an NFkB inhibitor remains controversial (recent data indicate that it may act via activation of AMPK).