INSIG1 and Insulin resistance: ,99 The AMPK signaling pathway is considered a sensor of the cellular energy state, which is activated by energy stress through rising AMP and/or ADP coupled with falling ATP, thereby regulating the metabolic state to maintain energy homeostasis.100, 101, 102, 103 AMPK activation inhibits acetyl-CoA carboxylase (ACC), reducing insulin resistance and hepatic steatosis.104, 105, 106 AMPK can also transcriptionally inhibit ACC by phosphorylating SREBP-1c and insulin-induced gene 1 (INSIG1).107