Deng Yalan, Dong Yuan, Zhang Sitian, Feng Yingmei
Department of Science and Technology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Laboratory for Clinical Medicine, Capital Medical University, Beijing, China.
Front Pharmacol. 2024 Sep 3;15:1463187. doi: 10.3389/fphar.2024.1463187. eCollection 2024.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and its prevalence is rapidly increasing. Antioxidants, lipid-lowering medications, and lifestyle interventions are the most commonly used treatment options for NAFLD, but their efficacy in inhibiting steatosis progression is limited and their long-term ineffectiveness and adverse effects have been widely reported. Therefore, it is important to gain a deeper understanding of the pathogenesis of NAFLD and to identify more effective therapeutic approaches. Mitochondrial homeostasis governs cellular redox biology, lipid metabolism, and cell death, all of which are crucial to control hepatic function. Recent findings have indicated that disruption of mitochondrial homeostasis occurs in the early stage of NAFLD and mitochondrial dysfunction reinforces disease progression. In this review, we summarize the physical roles of the mitochondria and describe their response and dysfunction in the context of NAFLD. We also discuss the drug targets associated with the mitochondria that are currently in the clinical trial phase of exploration. From our findings, we hope that the mitochondria may be a promising therapeutic target for the treatment of NAFLD.
非酒精性脂肪性肝病(NAFLD)是全球最常见的慢性肝病,其患病率正在迅速上升。抗氧化剂、降脂药物和生活方式干预是NAFLD最常用的治疗选择,但其抑制脂肪变性进展的疗效有限,且其长期无效性和不良反应已被广泛报道。因此,深入了解NAFLD的发病机制并确定更有效的治疗方法非常重要。线粒体稳态控制着细胞氧化还原生物学、脂质代谢和细胞死亡,所有这些对于控制肝功能都至关重要。最近的研究结果表明,线粒体稳态的破坏发生在NAFLD的早期阶段,线粒体功能障碍会加剧疾病进展。在这篇综述中,我们总结了线粒体的生理作用,并描述了它们在NAFLD背景下的反应和功能障碍。我们还讨论了目前处于临床试验探索阶段的与线粒体相关的药物靶点。基于我们的研究结果,我们希望线粒体可能成为治疗NAFLD的一个有前景的治疗靶点。