Jang Soo Yeon, Choi Kyung Mook
Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea.
J Cachexia Sarcopenia Muscle. 2025;16(4):e70000. doi: 10.1002/jcsm.70000.
Although the decline in muscle mass, function and increased visceral obesity are attracting substantial attention in the ageing society, approved treatment modalities for sarcopenia/sarcopenic obesity (SO) remain limited. Elucidating effects and mechanisms of adipose tissue and lipids on skeletal muscle is important for identifying potential prevention and treatment targets for sarcopenia/SO.
In this narrative review, we aim to comprehensively summarize current knowledge on how adipose tissue and lipid metabolites influence skeletal muscle with detailed mechanistic explanations, especially in sarcopenia development. We also tried to explore future perspectives for optimal strategies for managing sarcopenia.
Fatty infiltration in skeletal muscle can alter the structure, metabolism and signalling pathways of muscle, thereby worsening muscle function and physical performance. Intracellular lipid droplets could disrupt normal physiology within muscle cells, but it might be influenced not only by quantity but also by size, location and characteristics of lipid droplets. Intracellular lipid metabolites may induce lipotoxicity in cell signalling of muscle cells, but effects might differ by types or chemical structure. Highly trained athletes exhibit insulin sensitivity despite high levels of muscular fat, a phenomenon called the athlete's paradox. Lipid droplets within the skeletal muscle of athletes are small and are mainly located in the intermyofibrillar area, which is rich in fast-twitch, Type I fibres. In contrast, patients with Type 2 diabetes/obesity accumulate larger lipid droplets in the subsarcolemmal area, which is richer in Type II fibres. Ageing is intricately associated with mitochondrial dysfunction and the concomitant decline in mitochondrial biogenesis, all of which may lead to sarcopenia. SIRT1 and AMPK, two key energy sensors, are involved in mitochondrial biogenesis through regulation of PGC-1α. Modulation of PGC-1α levels in skeletal muscle may help protect against sarcopenia by preserving muscle integrity, enhancing muscle function, improving insulin sensitivity and reducing inflammation and oxidative stress. Excessive nutrient intake and obesity triggers mitochondrial dysfunction by inducing activation of the inflammatory response and increased production of reactive oxygen species. Skeletal muscle and adipose tissue are closely connected through mediators called adipokines and myokines, and it is important to understand the mechanisms of their interaction.
Dysregulation of lipid metabolism and intramuscular fat accumulation leads to inflammation, oxidative stress, insulin resistance and mitochondrial dysfunction, resulting in reduced muscle mass and strength. Further research on associations between fat/lipids and muscle would be helpful to investigate optimal management strategies for sarcopenia/SO in the rapidly ageing world.
尽管在老龄化社会中，肌肉质量下降、功能减退以及内脏肥胖增加引起了广泛关注，但目前获批用于治疗肌肉减少症/肌肉减少性肥胖（SO）的治疗方法仍然有限。阐明脂肪组织和脂质对骨骼肌的影响及机制，对于确定肌肉减少症/SO的潜在预防和治疗靶点至关重要。
在本叙述性综述中，我们旨在全面总结当前关于脂肪组织和脂质代谢产物如何影响骨骼肌的知识，并给出详细的机制解释，特别是在肌肉减少症发展过程中的情况。我们还试图探索管理肌肉减少症的最佳策略的未来前景。
骨骼肌中的脂肪浸润可改变肌肉的结构、代谢和信号通路，从而使肌肉功能和身体表现恶化。细胞内脂滴可能会破坏肌肉细胞内的正常生理功能，但这可能不仅受脂滴数量的影响，还受其大小、位置和特性的影响。细胞内脂质代谢产物可能会在肌肉细胞的信号传导中诱导脂毒性，但不同类型或化学结构的影响可能有所不同。训练有素的运动员尽管肌肉脂肪含量高，但仍表现出胰岛素敏感性，这种现象被称为运动员悖论。运动员骨骼肌中的脂滴较小，主要位于富含快肌纤维（I型纤维）的肌原纤维间区域。相比之下，2型糖尿病/肥胖患者在肌膜下区域积累更大的脂滴，该区域富含II型纤维。衰老与线粒体功能障碍以及随之而来的线粒体生物发生减少密切相关，所有这些都可能导致肌肉减少症。SIRT1和AMPK这两个关键的能量传感器，通过调节PGC-1α参与线粒体生物发生。调节骨骼肌中PGC-1α的水平，可能有助于通过维持肌肉完整性、增强肌肉功能、改善胰岛素敏感性以及减少炎症和氧化应激来预防肌肉减少症。营养摄入过多和肥胖通过诱导炎症反应激活和活性氧产生增加，引发线粒体功能障碍。骨骼肌和脂肪组织通过称为脂肪因子和肌因子的介质紧密相连，了解它们相互作用的机制很重要。
脂质代谢失调和肌肉内脂肪堆积会导致炎症、氧化应激、胰岛素抵抗和线粒体功能障碍，从而导致肌肉质量和力量下降。进一步研究脂肪/脂质与肌肉之间的关联，将有助于在快速老龄化的世界中探索肌肉减少症/SO的最佳管理策略。
