Targeting AMPK Signaling in the Liver: Implications for Obesity and Type 2 Diabetes Mellitus

Obesity and type 2 diabetes mellitus (T2DM), as common metabolic diseases, are pathologically characterized by overnutrition and insulin resistance (IR), which subsequently lead to glucose and lipid metabolism disorders. The liver, a major metabolic organ of the body, integrates hormone and metabolic signals to regulate the synthesis of lipids and glucose as well as their transport to peripheral tissues, hence playing an essential role in the development of obesity and T2DM. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a central regulator involved in cellular and organismal metabolism in eukaryotes, which activates processes that produce ATP and diminishes its consumption. In addition, AMPK also regulates mitochondrial homeostasis and promotes autophagy, both of which are associated with the pathogenesis of IR. Therefore, increasing AMPK activity is considered a promising therapeutic strategy to prevent obesity and T2DM. In this review, we summarize the role of hepatic AMPK in obesity and T2DM and the potential of using AMPK activators as therapeutics for metabolic disorders.