MicroRNA regulation of AMPK in nonalcoholic fatty liver disease

Obesity-associated nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is the leading cause of liver failure and death. The function of AMP-activated protein kinase (AMPK), a master energy sensor, is aberrantly reduced in NAFLD, but the underlying mechanisms are not fully understood. Increasing evidence indicates that aberrantly expressed microRNAs (miRs) are associated with impaired AMPK function in obesity and NAFLD. In this review, we discuss the emerging evidence that miRs have a role in reducing AMPK activity in NAFLD and nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. We also discuss the underlying mechanisms of the aberrant expression of miRs that can negatively impact AMPK, as well as the therapeutic potential of targeting the miR-AMPK pathway for NAFLD/NASH. MicroRNAs that regulate the activity of a master energy-sensing protein in the cell offer promising therapeutic targets for the treatment of chronic liver disease. Hao Sun and Jongsook Kim Kemper from the University of Illinois at Urbana-Champaign, USA, review how aberrantly expressed microRNAs contribute to the impaired function of AMP-activated protein kinase (AMPK), an energy-sensing protein crucial for various metabolic processes in the liver. Such microRNAs directly target AMPK subunits and indirectly affect signaling pathways. In conditions associated with obesity, imbalanced microRNA expression leads to reduced AMPK activity, resulting in fat accumulation in the liver, impaired glucose metabolism, increased inflammation, and oxidative stress. Restoring normal microRNA levels through drugs holds potential for reversing the symptoms of nonalcoholic fatty liver disease, which can progress to the severe disease known as nonalcoholic steatohepatitis.