癌症恶病质（瘦体重的无意损失）会导致功能依赖、治疗结果不佳和生存率下降。虽然其致病性是多因素的，但代谢功能障碍仍然是恶病质的一个标志。然而，在了解骨骼肌脂质代谢和动力学在这种情况下的作用方面存在重大知识差距。我们使用路易斯肺癌 (LLC) 鼠恶病质模型检查了骨骼肌代谢功能障碍、肌细胞内 LD 含量、LD 形态和亚细胞分布以及 LD-线粒体相互作用。 C57/BL6 雄性小鼠 (n=20) 在右胁腹植入 LLC 细胞 [106] 或接受 PBS 假注射。切除骨骼肌用于透射电子显微镜检查（TEM；比目鱼肌）、油红o/脂质染色（胫骨前肌）和蛋白质（腓肠肌）。 LLC 小鼠的肌细胞内 LD 数量较多（232%；p=0.006），尺寸较大（130%；p=0.023），这进一步得到油红 O 阳性增加（87%；p=0.0109）和“非常高”油的支持。 -与对照相比，红O阳性（178%；p=0.0002）纤维，这与纤维尺寸呈负相关（R2=0.5294；p<0.0001）。 LD 的形态分析显示，伸长率和复杂性增加（纵横比：IMF：9%，p=0.046），圆度（圆度：SS：6%，p=0.042）或圆度（圆度：整体：10%，p= 0.033；IMF：8%，p=0.038）以及 LD 线粒体接触减少（-15%；p=0.006）、接触长度（-38%；p=0.036）和相对接触（86%；p= 0.004）。此外，还观察到恶病质肌肉中脂质代谢（脂联素、CPT-1b）和 LD 相关蛋白、perilipin-2 和 perilipin-5 的失调（p<0.05）。总的来说，我们提供的证据表明，在癌症恶病质的临床前模型中发生了骨骼肌肌脂肪变性、LD 形态改变和 LD-线粒体相互作用减少。

Cancer cachexia, the unintentional loss of lean mass, contributes to functional dependency, poor treatment outcomes, and decreased survival. While its pathogenicity is multifactorial, metabolic dysfunction remains a hallmark of cachexia. However, significant knowledge gaps exist in understanding the role of skeletal muscle lipid metabolism and dynamics in this condition. We examined skeletal muscle metabolic dysfunction, intramyocellular LD content, LD morphology and subcellular distribution, and LD-mitochondrial interactions using the Lewis Lung Carcinoma (LLC) murine model of cachexia. C57/BL6 male mice (n=20) were implanted with LLC cells [106] in the right flank or underwent PBS sham injections. Skeletal muscle was excised for transmission electron microscopy (TEM; soleus), oil red o/lipid staining (tibialis anterior), and protein (gastrocnemius). LLC mice had a greater number (232%; p=0.006) and size (130%; p=0.023) of intramyocellular LDs further supported by increased oil-red O positive (87%; p=0.0109) and 'very high' oil-red O positive (178%; p=0.0002) fibers compared to controls and this was inversely correlated with fiber size (R2=0.5294; p<0.0001). Morphological analyses of LDs show increased elongation and complexity (aspect ratio: IMF: 9%, p=0.046) with decreases in circularity (circularity: SS: 6%, p=0.042) or roundness (roundness: Whole: 10%, p=0.033; IMF: 8%, p=0.038) as well as decreased LD-mitochondria touch (-15%; p=0.006), contact length (-38%; p=0.036), and relative contact (86%; p=0.004). Further, dysregulation in lipid metabolism (adiponectin, CPT-1b) and LD-associated proteins, perilipin-2 and perilipin-5, in cachectic muscle (p<0.05) were observed. Collectively, we provide evidence that skeletal muscle myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in a preclinical model of cancer cachexia.