劉德中施玉惠Yu-Hui Shih營養學研究所2026-03-249999/12/312015https://handle.ncl.edu.tw/11296/kauf76https://scholars.csmu.edu.tw/handle/123456789/6977癌症惡病質(Cancer cachexia)為代謝性症狀的疾病，有體重減輕及骨骼肌大量流失症狀，常發生在癌症末期病患身上，大幅增加癌症病患死亡率。中鏈三酸甘油酯（medium-chain triglycerides，MCT）為碳鏈介於6-14的飽和脂肪酸所構成的三酸甘油酯。因中鏈脂肪酸在被小腸吸收後可直接經由肝門靜脈進入肝臟，相較於長鏈脂肪酸，中鏈脂肪酸易被體內代謝及利用產生熱量，故臨床上常以MCT作為重症病患營養補充，產生熱量。文獻指出，高MCT的生酮飲食，可減少癌症惡病質病患的體重流失，但補充MCT是否可對抗癌症惡病質所誘發的肌肉萎縮仍是未知的。本實驗目的是探討補充MCT是否可抑制癌症惡病質所引起的肌肉流失。本實驗使用路易斯氏肺癌細胞（Lewis lung carcinoma，LLC）來誘發C57BL/6小鼠癌症及肌肉萎縮，評估相較於給予沙拉油的補充，補充MCT是否可減少肺癌細胞誘發小鼠後腿骨骼肌肉流失及相關機制。觀察到相較於給予沙拉油的補充，補充MCT可減少腫瘤小鼠體重、骨骼肌及脂肪組織的流失，以及降低腫瘤重量。使用ELISA kit檢測發現，補充MCT可減少腫瘤小鼠血漿中TNF-α和IL-6的含量。以即時定量reverse transcription- polymerase chain reaction及西方墨點法分析腫瘤小鼠腓腸肌中肌肉蛋白指標myosin heavy chain（MyHC）的mRNA與蛋白質表現量發現，補充MCT可顯著抑制腫瘤小鼠腓腸肌MyHC的流失。此外，補充MCT可顯著抑制腫瘤小鼠肌肉中泛素-蛋白酶體路徑(ubiquitin- proteasome pathway)、自噬作用-溶酶體途徑(autophagy-lysosome pathway)相關路徑基因與蛋白質表現量以及降低cleavage caspase-3的蛋白質表現量。MCT的補充可顯著增加腫瘤小鼠肌肉細胞質內protein kinase B及forkhead box O transcription factors (FoxOs)磷酸化蛋白質表現，及抑制細胞核內的FoxOs表現量。補充MCT不影響腫瘤小鼠肌肉adenosine monophosphate-activated protein kinase、inhibitor -kappa B-a及mitogen-activated protein kinases以及細胞核內CCAAT/enhancer binding protein B (C/EBP B)與nucler factor-kappa B (NF-kB)蛋白質表現。另外，免疫組織染色亦發現補充MCT可顯著減少腫瘤小鼠肌肉細胞核內FoxOs表現但不影響細胞核C/EBP B及NF-kB的蛋白質表現。綜合以上可知，補充MCT可抑制腫瘤小鼠血漿中TNF-a和IL-6的表現，抑制發炎反應。此外，補充MCT可經由減少癌細胞所誘發FoxOs轉錄活性進而減少泛素-蛋白酶體及自噬作用-溶酶體途徑相關蛋白質表現，及抑制腫瘤小鼠肌肉中caspase- 3的活化，減少癌細胞所誘發骨骼肌肉蛋白流失，改善癌症惡病質造成的肌肉萎縮現象。Cancer cachexia is a metabolic syndrome relevant to the progressive loss of body weight and skeletal muscle mass. Cancer cachexia occurs in advanced cancer patients and associated with the elevation of morbidity and mortality of cancer patients. Medium-chain triglycerides (MCT), the saturated fatty acids with a chain length of 6–14 carbons, are absorbed and transported directly into the liver via the portal vein, which increase the metabolism and utilization of fatty acids. For this reason, MCT are often used in clinical nutrition intervention for critically ill patients. It has been reported that MCT-rich high fat diet could prevent weight loss in cancer cachexia patients. However, whether MCT resists cachexia- induced muscle atrophy is unknown. The objective of this study is to investigate the inhibitory effect of MCT on muscle wasting induced by the cancer cells. In our study, we assessed the effect of MCTs on Lewis lung carcinoma cells (LLC) induced muscle wasting in C57BL/6 mice. We observed that MCT reduced the loss of body weight, muscle mass and adipose tissue, as well as decreased tumor mass in tumor-bearing mice compare with Soybean oil. Supplementation of MCT can reduce the content of plasma interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in tumor mice by ELISA kit. Data from real-time quantitative reverse transcription-polymerase chain reaction and western blot analysis showed that MCT supplementation could effectively inhibit ubiquitin-proteasome pathway (UPP) and autophagy-lysosome pathway (ALP) related protein expression as well as nuclear FoxOs (forkhead box O transcription factors) amount in gastrocnemius muscle of tumor-bearing mice compare with Soybean oil supplementation. However, MCT supplement does not affect tumor mouse muscle adenosine monophosphate-activated protein kinase, inhibitor-kappaB-α and mitogen-activated protein kinases as well as nuclear CCAAT/enhancer binding protein B (C/EBP B) and nuclear factor-kappa B (NF-kB) protein expression. In addition, immunohistochemical staining was also found that MCT supplement can significantly reduce muscle nucleus FoxOs but does not C/ C/EBP B and NF-kB in the muscle of tumor-bearing mice. summarily, MCT supplementation inhibit plasma TNF-a and IL-6 in tumor bearing mice. In addition, supplementary MCT through the dcrease in FoxOs transcriptional activity by cancer cell inhibited the UPP and ALP related protein expression, and activation of caspase-3, which resulted in prevention of cancer induced- skeletal muscle wasting癌症惡病質肌肉萎縮中鏈三酸甘油酯泛素化-蛋白&#37238體途徑自噬作用-溶&#37238caner cachexiamuscle atrophyMedium-chain triglyceridesubiquitin-proteasome pathwayautophagy- lysosome pathwaythesis