PO.MCB09.04 · 分子与细胞生物学
通过运动训练重新平衡慢性淋巴细胞白血病中的全身及细胞能量代谢紊乱
Rebalancing systemic and cellular energy dysmetabolism in Chronic Lymphocytic Leukemia through exercise training
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：慢性淋巴细胞白血病（CLL）细胞异常表达脂蛋白脂肪酶（LPL），该酶通常仅限于脂肪细胞和肌细胞中用于脂质介导的能量利用。这使得CLL细胞能够储存和利用脂质，可能与健康组织竞争或从中转移资源。体外研究表明，降低脂肪酸的可用性可能限制CLL增殖；然而，对于患者如何在体内调控这一过程知之甚少。运动训练提供了一种全身性、非药物性的方法来对抗代谢失调，对肿瘤控制和整体健康具有潜在益处。
方法：我们开展了一项为期12周的运动试验，纳入五名初治（TN-CLL）和五名既往接受过治疗（Td-CLL）的患者。我们评估了摄入脂质在项目前（基线）和项目后（干预后）的代谢去向。患者食用含200mg棕榈酸示踪剂（13CPA）的餐食，并每小时采集血样，持续3小时（T0h-T3h）。我们使用质谱法评估血浆三酰甘油（TAG）和非酯化脂肪酸（NEFA）中的13CPA富集以及免疫细胞（PBMC）中的总脂肪酸，数据采用RM-ANOVA进行分析。
结果：餐后摄入后，血浆TAG和NEFA中的13CPA富集从T1h-T3h稳步增加（p<0.001）。在基线T3h时，TN-CLL表现出比Td-CLL更高的血浆13CPA-TAG和未标记PA-TAG掺入（p<0.001）。干预后T3h时，TN-CLL的13CPA-TAG水平下降（p<0.05），且不再与Td-CLL有显著差异。与Td-CLL相比，TN-CLL的13CPA-NEFA富集在干预后增加（p<0.05），提示13CPA-TAG水解增强。同样，13CPA摄入到PBMC中——在基线T3h时TN-CLL中更高（p<0.05）——在干预后减少。
结论：这项试点研究证明了使用稳定同位素示踪评估CLL体内脂质摄取的可行性。TN-CLL患者的运动训练减少了脂质摄取，提示向更平衡、更健康的代谢特征转变。需要进一步研究以确定运动是否能够破坏CLL细胞对脂质的依赖。
查看英文原文 English abstract
Introduction : Chronic lymphocytic leukaemia (CLL) cells abnormally express lipoprotein lipase (LPL), an enzyme typically restricted to adipocytes and myocytes for lipid-mediated energy utilisation. This enables CLL cells to store and utilise lipids, potentially competing with or diverting resources from healthy tissues. In vitro studies suggest that reducing fatty acid availability may limit CLL proliferation; however, little is known about how patients can modulate this process in vivo . Exercise training offers a systemic, non-pharmacological approach to counter metabolic dysregulation, with potential benefits for tumour control and overall health.
Methods : We conducted a 12-week exercise trial involving five treatment-naive (TN-CLL) and five previously treated (Td-CLL) patients. We assessed the metabolic fate of ingested lipids before (Baseline) and after (Post-Intervention) the program. Patients consumed a meal containing 200mg palmitic acid tracer ( 13 CPA), and blood samples were collected hourly for 3 hours (T 0h -T 3h ). We assessed 13 CPA enrichment in plasma triacylglycerol (TAG) and non-esterified fatty acids (NEFA), and total fatty acids in immune cells (PBMC) using mass spectrometry, and data were analysed using RM-ANOVA.
Results : Post-meal ingestion, 13 CPA enrichment in plasma TAG and NEFA increased steadily from T 1h -T 3h (p<0.001). At Baseline T 3h , TN-CLL exhibited higher plasma 13 CPA-TAG and unlabelled PA-TAG incorporation than Td-CLL (p<0.001). Post-Intervention T 3h , TN-CLL 13 CPA-TAG levels decreased (p<0.05) and were no longer significantly different than Td-CLL. TN-CLL 13 CPA-NEFA enrichment increased post-Intervention compared to Td-CLL (p<0.05), suggesting enhanced 13 CPA-TAG hydrolysis. Similarly, 13 CPA uptake into PBMCs, which was higher in TN-CLL at Baseline T 3h (p<0.05), reduced Post-intervention.
Conclusion : This pilot study demonstrates the feasibility of stable isotope tracing to assess in vivo lipid uptake in CLL. Exercise training in TN-CLL patients reduced lipid uptake, suggesting a shift towards a more balanced and healthier metabolic profile. Further research is needed to determine whether exercise can disrupt the lipid dependence of CLL cells.
利益披露 Disclosure
U. Zaheer, None..
E. Miles, None..
A. Avramovska, None..
V. Srikumaran, None..
A. Hulton, None..
L. Li, None..
C. Jeary, None..
A. Sitlinger, None..
R. Walewska, None..
B. Fielding, None..
D. Bartlett, None.