AMP-activated protein kinase (AMPK) is a cellular energy sensor which plays a crucial role in regulation of whole-body energy homeostasis. Activation of AMPK signaling results in favorable effects on mitochondrial function, autophagy, glucose/lipid metabolism, and insulin sensitivity, making it an important therapeutic target in treatment/prevention of metabolic disorders and cancer. Recently, pharmacological studies of natural phenolic compounds indicated that the benefits on metabolic health of these phytochemicals are not only related to their protogenic antioxidant property but also to their AMPK-activating potential. Due to their diverse structures, identification of phenolic compound molecules which have potential to target the AMPK activation for beneficial metabolic effects may be promising in order to develop novel therapeutics in the prevention and/or treatment of metabolic disorders. In this minireview, we summarize beneficial metabolic outcomes of AMPK activation and discuss the capability of natural polyphenols to activate the AMPK pathway focusing on the phenolic acids as potential lead compounds.
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