Cachexia-induced reprogramming of visceral organ metabolism by human pancreatic cancer xenografts

We have uploaded the raw MRS data used in this study. The data were obtained through dual-phase extraction from the heart, lungs, kidneys, pancreas, liver, and spleen samples. Each sample was reconstituted in 650 μL of phosphate-buffered D₂O (90:10 D₂O:H₂O, pH 7.4) with trimethylsilylpropanoic acid (TSP), and analyzed by ¹H MRS.All spectra were acquired using a Bruker 750 MHz NMR spectrometer using single pulse sequence under consistent experimental conditions: a spectral width of 15,495.86 Hz, 64K data points, a 90° flip angle, a relaxation delay of 10 seconds, an acquisition time of 2.11 seconds, and 64 scans with 8 dummy scans. The MRS data were analyzed and quantified using TOPSPIN 4.0.6 software. Spectral processing included zero-filling to 64K and applying an exponential line broadening of 0.3 Hz before Fourier transformation. Peak integration was performed using AMIX software, and the area under each peak was used for quantitative analysis after normalization to the internal standard, TSP (trimethylsilylpropanoic acid). We identified, for the first time, the profound effects of pancreatic cancer induced cachexia on visceral organ weight and metabolism that can lead to severe consequences in organ function ranging from affecting pathways involved in tissue regeneration and resolving inflammation, to altering IL-4 production in cachectic mice. These results highlight the damaging systemic changes in visceral organ metabolism that occur with cancer induced cachexia that may lead to metabolic interventions to reduce morbidity and mortality.本研究所使用的原始磁共振波谱（Magnetic Resonance Spectroscopy, MRS）数据已上传。该数据通过对心脏、肺、肾、胰腺、肝脏及脾脏样本进行双相萃取获取。每份样本均用含三甲基硅基丙酸（TSP）的650 μL磷酸盐缓冲氘水（体积比90:10的D₂O:H₂O，pH 7.4）复溶，随后通过氢质子磁共振波谱（¹H MRS）进行分析。所有波谱均采用布鲁克750 MHz核磁共振波谱仪，以单脉冲序列在统一实验条件下采集：谱宽15495.86 Hz，数据点数64K，90°翻转角，弛豫延迟10秒，采集时间2.11秒，扫描次数64次，预扫描8次。磁共振波谱数据采用TOPSPIN 4.0.6软件进行分析与定量。波谱处理步骤包括：将数据零填充至64K，并在傅里叶变换前施加0.3 Hz的指数线宽增宽。采用AMIX软件进行峰积分，将每个峰的峰面积归一化至内标TSP（三甲基硅基丙酸）后，用于定量分析。本研究首次揭示了胰腺癌诱导恶病质对内脏器官重量与代谢的显著影响：其可对器官功能造成严重不良后果，影响范围涵盖组织再生相关通路、炎症消退过程，以及改变恶病质小鼠体内白细胞介素4（IL-4）的产生。上述结果凸显了癌症诱导恶病质引发的内脏器官代谢系统性损伤性改变，该发现可为通过代谢干预手段降低发病率与死亡率提供理论依据。