Choi Jae Yeon, Kim Ye Jin, Shin Jeong Seob, Choi EunBi, Kim Yuhyun, Kim Min Gwan, Kim Yang Tae, Park Byong Seo, Kim Jae Kwang, Kim Jae Geun
Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea.
Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea; Research Center of Brain-Machine Interface, Incheon National University, Incheon, 22012, Republic of Korea.
Biochem Biophys Res Commun. 2025 May 12;763:151766. doi: 10.1016/j.bbrc.2025.151766. Epub 2025 Apr 5.
Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive weight loss, muscle wasting, and systemic inflammation. Despite its clinical significance, the underlying mechanisms linking central and peripheral metabolic changes remain incompletely understood. In this study, we employed a murine model of cancer cachexia induced by intraperitoneal injection of Lewis lung carcinoma (LLC1) cells to investigate tissue-specific metabolic adaptations. Cachectic mice exhibited reduced food intake, body weight loss, impaired thermoregulation, and decreased energy expenditure. Metabolomic profiling of serum, skeletal muscle, and hypothalamus revealed distinct metabolic shifts, with increased fatty acid and ketone body utilization and altered amino acid metabolism. Notably, hypothalamic metabolite changes diverged from peripheral tissues, showing decreased neurotransmitter-related metabolites and enhanced lipid-based energy signatures. Gene expression analysis further confirmed upregulation of glycolysis- and lipid oxidation-related genes in both hypothalamus and muscle. These findings highlight coordinated yet compartmentalized metabolic remodeling in cancer cachexia and suggest that hypothalamic adaptations may play a central role in the systemic energy imbalance associated with cachexia progression.
癌症恶病质是一种多因素代谢综合征，其特征为进行性体重减轻、肌肉消耗和全身炎症。尽管其具有临床意义，但连接中枢和外周代谢变化的潜在机制仍未完全阐明。在本研究中，我们采用腹腔注射刘易斯肺癌（LLC1）细胞诱导的癌症恶病质小鼠模型来研究组织特异性代谢适应性。恶病质小鼠表现出食物摄入量减少、体重减轻、体温调节受损和能量消耗降低。血清、骨骼肌和下丘脑的代谢组学分析揭示了明显的代谢变化，脂肪酸和酮体利用增加，氨基酸代谢改变。值得注意的是，下丘脑代谢物变化与外周组织不同，神经递质相关代谢物减少，脂质能量特征增强。基因表达分析进一步证实下丘脑和肌肉中糖酵解和脂质氧化相关基因上调。这些发现突出了癌症恶病质中协调但分区的代谢重塑，并表明下丘脑适应性可能在与恶病质进展相关的全身能量失衡中起核心作用。
