Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?

Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?
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DOI:
10.1007/s00726-012-1221-2
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发表时间:
2012-10-01
期刊:
影响因子:
3.5
通讯作者:
Blachier, Francois
Blachier, Francois
中科院分区:
生物学3区
文献类型:
--
作者:
Boutry, Claire;Matsumoto, Hideki;Blachier, Francois

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内毒素血症影响肠道生理。循环中瓜氨酸浓度的降低被认为是肠道功能的反映。瓜氨酸可以在肠道细胞中产生,尤其是谷氨酸和谷氨酰胺。这项工作的目的是确定内毒素血症是否会降低血液、肠道和肌肉中的谷氨酸、谷氨酰胺和瓜氨酸的浓度,以及补充谷氨酸或谷氨酰胺是否可以恢复正常浓度。以0.3 mg·kg~(-1)脂多糖(LPS)腹腔注射诱导大鼠内毒素血症。这导致了迅速的厌食症,负氮平衡和一过性循环中IL-6和TNF-α水平的升高。与配对喂养(PF)动物的测量值相比,包括瓜氨酸在内的几乎所有循环氨基酸(AA)都下降,表明肠道功能下降。然而,在注射内毒素后D2,大多数循环AA浓度接近于PF组的记录值。当时,在AA中,只有腓肠肌中的谷氨酸、谷氨酰胺和瓜氨酸降低,而肠粘膜没有变化。补充4%的谷氨酸钠(MSG)或等摩尔量的谷氨酰胺不能恢复血浆和肌肉中谷氨酸、谷氨酰胺和瓜氨酸的浓度。然而,补充味精会导致谷氨酸在肠粘膜中积累。总之,内毒素血症迅速但短暂地降低了肌肉中几乎所有AA以及更持久的谷氨酸、谷氨酰胺和瓜氨酸的循环浓度。补充谷氨酸或谷氨酰胺不能恢复血浆和肌肉中谷氨酸、谷氨酰胺和瓜氨酸的浓度。讨论了内毒素血症时肠道对AA的吸收和/或代谢能力的丧失(从瓜氨酸血浆浓度下降判断)的含义,以解释这种结果。
Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine. The aim of this work was to determine if glutamate, glutamine and citrulline concentrations in blood, intestine and muscle are decreased by endotoxemia, and if supplementation with glutamate or glutamine can restore normal concentrations. We induced endotoxemia in rats by an intraperitoneal injection of 0.3 mg kg(-1) lipopolysaccharide (LPS). This led to a rapid anorexia, negative nitrogen balance and a transient increase of the circulating level of IL-6 and TNF-alpha. When compared with the values measured in pair fed (PF) animals, almost all circulating amino acids (AA) including citrulline decreased, suggesting a decrease of intestinal function. However, at D2 after LPS injection, most circulating AA concentrations were closed to the values recorded in the PF group. At that time, among AA, only glutamate, glutamine and citrulline were decreased in gastrocnemius muscle without change in intestinal mucosa. A supplementation with 4% monosodium glutamate (MSG) or an isomolar amount of glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscle. However, MSG supplementation led to an accumulation of glutamate in the intestinal mucosa. In conclusion, endotoxemia rapidly but transiently decreased the circulating concentrations of almost all AA and more durably of glutamate, glutamine and citrulline in muscle. Supplementation with glutamate or glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscles. The implication of a loss of the intestinal capacity for AA absorption and/or metabolism in endotoxemia (as judged from decreased citrulline plasma concentration) for explaining such results are discussed.