AMPK and SIRT1 both activate each other and diminish oxidative and ER stress and low-grade inflammation in various settings. Conversely, oxidative and ER stress and inflammation, which activate each other, appear to diminish AMPK and SIRT1. In principle, any of these factors could be targeted to combat IR and the development of metabolic syndrome–associated disorders; however, to date, the most success has been observed with therapies that target AMPK.