McCaffrey Jonas M, Ibdah Jamal A
School of Medicine, University of Missouri, Columbia, MO 65212, USA.
Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USA.
Nutrients. 2025 Sep 16;17(18):2972. doi: 10.3390/nu17182972.
Metabolic dysfunction-associated steatotic liver disease (MASLD) impacts nearly a quarter of the world's population and encompasses a range of disease states, from simple steatosis to more advanced stages like metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis. A key driver of disease progression is mitochondrial dysfunction, characterized by impaired fatty acid oxidation and an overall decline in mitochondrial health. Emerging evidence has implicated ceramides-bioactive sphingolipids that serve roles in apoptotic pathways and as signals of nutrient excess-as important contributors to this dysfunction. Ceramide accumulation within mitochondria mirrors impairments seen in MASLD, specifically elevations in oxidative stress, disrupted fatty acid oxidation, and impaired mitochondrial dynamics. Ceramides may serve as an important molecular link between nutrient overload and mitochondrial dysfunction in the pathogenesis of MASLD. Given the limited availability of effective pharmacologic therapies for MASLD, lifestyle interventions like dietary modification and physical activity remain the cornerstone of disease management worldwide. In this review, we provide an overview of the current understanding of the role of ceramides in mediating the effects of diet and exercise on MASLD through their influence on mitochondrial health.
代谢功能障碍相关脂肪性肝病（MASLD）影响着全球近四分之一的人口，涵盖了一系列疾病状态，从单纯性脂肪变性到更晚期的阶段，如代谢功能障碍相关脂肪性肝炎（MASH）、纤维化和肝硬化。疾病进展的一个关键驱动因素是线粒体功能障碍，其特征是脂肪酸氧化受损和线粒体健康状况整体下降。新出现的证据表明，神经酰胺——在细胞凋亡途径中起作用且作为营养过剩信号的生物活性鞘脂——是这种功能障碍的重要促成因素。线粒体中神经酰胺的积累反映了MASLD中出现的损伤，特别是氧化应激升高、脂肪酸氧化中断和线粒体动力学受损。在MASLD的发病机制中，神经酰胺可能是营养过载与线粒体功能障碍之间的重要分子联系。鉴于针对MASLD的有效药物治疗有限，饮食调整和体育锻炼等生活方式干预仍然是全球疾病管理的基石。在这篇综述中，我们概述了目前对神经酰胺在介导饮食和运动对MASLD的影响中所起作用的理解，这种影响是通过它们对线粒体健康的作用实现的。
