Palomer Xavier, Wang Jue-Rui, Escalona Claudia, Wu Siyuan, Wahli Walter, Vázquez-Carrera Manuel
Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona, 08028 Barcelona, Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain; Pediatric Research Institute, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Barcelona, Spain.
Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland; ToxAlim (Research Center in Food Toxicology), Institut National de Recherche pour l'Agriculture, l'Alimentation, et l'Environnement (INRAE), Unité Mixte de Recherche (UMR) 1331, F-31300 Toulouse Cedex, France.
Trends Pharmacol Sci. 2025 Jun;46(6):551-566. doi: 10.1016/j.tips.2025.03.008. Epub 2025 Apr 28.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and often progresses to hepatic fibrosis, cirrhosis, and liver failure. Despite its increasing prevalence, effective pharmacological treatments for MASLD-related fibrosis remain limited. Recent research has highlighted AMP-activated protein kinase (AMPK) as a key regulator of the processes that promote fibrogenesis, and AMPK activation shows potential in mitigating fibrosis. Advances in AMPK activators and deeper insights into their role in fibrotic pathways have recently revitalized interest in targeting AMPK for fibrosis treatment. This review discusses the molecular mechanisms linking AMPK to hepatic fibrosis and evaluates emerging AMPK-directed therapies. Furthermore, it addresses challenges in clinical translation. Importantly, we combine the latest mechanistic discoveries with recent therapeutic developments to provide a comprehensive perspective on AMPK as a target for hepatic fibrosis treatment.
代谢功能障碍相关脂肪性肝病(MASLD)是最常见的慢性肝病,常进展为肝纤维化、肝硬化和肝衰竭。尽管其患病率不断上升,但针对MASLD相关纤维化的有效药物治疗仍然有限。最近的研究强调,AMP激活的蛋白激酶(AMPK)是促进纤维化过程的关键调节因子,AMPK激活在减轻纤维化方面显示出潜力。AMPK激活剂的进展以及对其在纤维化途径中作用的更深入了解,最近重新激发了针对AMPK进行纤维化治疗的兴趣。本综述讨论了将AMPK与肝纤维化联系起来的分子机制,并评估了新兴的针对AMPK的疗法。此外,还探讨了临床转化中的挑战。重要的是,我们将最新的机制发现与近期的治疗进展相结合,以全面阐述AMPK作为肝纤维化治疗靶点的情况。