Department of Molecular and Integrative Physiology, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Exp Mol Med. 2023 Sep;55(9):1974-1981. doi: 10.1038/s12276-023-01072-3. Epub 2023 Sep 1.
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.
肥胖相关性非酒精性脂肪性肝病(NAFLD)是最常见的慢性肝病,也是肝衰竭和死亡的主要原因。AMP 激活的蛋白激酶(AMPK)作为一种主要的能量感受器,其功能在 NAFLD 中异常降低,但潜在机制尚不完全清楚。越来越多的证据表明,异常表达的 microRNAs(miRs)与肥胖和非酒精性脂肪性肝炎(NASH)中 AMPK 功能受损有关,NASH 是 NAFLD 的一种严重形式。本文讨论了 miR 在降低 NAFLD 和 NASH 中 AMPK 活性中的作用的新证据,也讨论了 miR 异常表达对 AMPK 产生负面影响的潜在机制,以及针对 miR-AMPK 通路治疗 NAFLD/NASH 的潜在可能性。