Laboratory of Biological Nutrition, EA 4466, Paris Descartes University, Paris, France.
J Appl Physiol (1985). 2013 Jul 15;115(2):229-34. doi: 10.1152/japplphysiol.01230.2012. Epub 2013 May 2.
Dietary leucine (Leu) serves as a nitrogen donor for de novo glutamine (Gln) synthesis in muscle. However, aging is characterized by an increase in the splanchnic extraction of Leu (SPELeu), i.e., splanchnic sequestration (SSLeu), which may affect muscle Gln metabolism and its subsequent homeostasis at the whole-body level. The aim of the work was to assess the effect of age-related SSLeu on Gln metabolism in the muscle, gut, liver, kidney, and Gln exchanges among these organs during fed conditions. Young-adult (3-mo-old) or aged (24-mo-old), male Sprague-Dawley rats were studied during fed condition [infusion of amino acids (AA) into the duodenum from time 0 min (T0) to T60] under anesthesia. L-[5-(15)N]Gln and L[1-(13)C]Leu were infused into the jugular vein and L-[5,5,5-(2)H3]Leu into the duodenum. At T60, blood samples were taken from carotid artery, portal vein, hepatic vein, renal vein, and inferior vena cava for tracer-tracee ratio and AA level measurements. SSLeu was observed in old rats and was negatively correlated with muscle Gln production (r = -0.501, P < 0.01). In addition, reduced Gln muscle release in old rats was accompanied by reduced Gln uptake by the gut and kidney. However, net Gln balance across organs was not different between young adult and old rats. During fed conditions in old rats, muscle Gln production and release are reduced in relation to the observed, increased SPELeu and reduced renal and intestinal Gln uptake to maintain whole-body Gln homeostasis. Our results demonstrate the existence of an age-related change of interorgan Gln metabolism, which may be, in part, driven by SSLeu.
饮食中的亮氨酸（Leu）可作为肌肉中从头合成谷氨酰胺（Gln）的氮供体。然而，衰老是以内脏亮氨酸提取（SPELeu）增加为特征的，即内脏隔离（SSLeu），这可能会影响肌肉 Gln 代谢及其在全身水平上的随后内稳态。本研究旨在评估与年龄相关的 SSLeu 对喂养条件下肌肉、肠道、肝脏、肾脏中 Gln 代谢及其器官间 Gln 交换的影响。在麻醉下，研究了年轻成年（3 月龄）或老年（24 月龄）雄性 Sprague-Dawley 大鼠在喂养条件下（从 T0 到 T60 时十二指肠氨基酸[AA]输注）的情况。L-[5-(15)N]Gln 和 L[1-(13)C]Leu 静脉内输注，L-[5,5,5-(2)H3]Leu 十二指肠内输注。在 T60 时，从颈总动脉、门静脉、肝静脉、肾静脉和下腔静脉取血样，进行示踪剂-示踪物比和 AA 水平测定。在老年大鼠中观察到 SSLeu，其与肌肉 Gln 生成呈负相关（r = -0.501，P < 0.01）。此外，老年大鼠肌肉 Gln 释放减少伴随着肠道和肾脏 Gln 摄取减少。然而，年轻成年和老年大鼠各器官间 Gln 净平衡无差异。在老年大鼠的喂养条件下，肌肉 Gln 生成和释放减少与观察到的增加的 SPELeu 和减少的肾和肠 Gln 摄取有关，以维持全身 Gln 内稳态。我们的结果表明，存在与年龄相关的器官间 Gln 代谢变化，其可能部分由 SSLeu 驱动。
