Buijs Nikki, Vermeulen Mechteld A R, Weeda Viola B, Bading James R, Houdijk Alexander P J, van Leeuwen Paul A M
a Department of Surgery , VU University Medical Center , Amsterdam , The Netherlands and Department of Surgery , Medical Center Alkmaar, Trial Center Holland Health , Alkmaar , The Netherlands.
Nutr Cancer. 2015;67(5):713-20. doi: 10.1080/01635581.2015.1029638. Epub 2015 Apr 16.
Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.
恶性肿瘤会促使精氨酸（免疫系统的一种重要底物）被消耗。为维持免疫功能，荷瘤宿主通过动员骨骼肌中的谷氨酰胺来加速精氨酸的肠 - 肾轴循环，这可能会促进恶病质。补充谷氨酰胺可刺激健康受试者体内精氨酸的生成。精氨酸的肠 - 肾轴以及补充谷氨酰胺对癌症恶病质的影响尚未得到研究。本研究评估了恶病质发生后精氨酸生成的器官间途径的长期适应性变化以及补充谷氨酰胺在恶病质状态下的代谢效应。将Fischer - 344大鼠随机分为荷瘤组（n = 12）、对照组（n = 7）和接受富含谷氨酰胺饮食的荷瘤组（n = 9）。研究了氨基酸在肠道、肾脏和肝脏中的通量以及净分数提取量。与对照组相比，荷瘤大鼠的门静脉引流脏器摄取的谷氨酰胺显著增多，而释放的瓜氨酸显著减少。与对照组相比，恶病质荷瘤大鼠的肾脏代谢没有变化。补充谷氨酰胺对肠道和肾脏的适应性没有影响。总之，在恶病质状态下，肠道对谷氨酰胺摄取的增加并未伴随着肾脏精氨酸生成的增加。在恶病质荷瘤大鼠中发现的适应性变化并不依赖于谷氨酰胺的可用性。
