l-Citrulline supplementation improves glucose and exercise tolerance in obese male mice
l-Citrulline supplementation improves glucose and exercise tolerance in obese male mice
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DOI：
10.1113/ep088109
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发表时间：
2020-01-15
影响因子：
2.7
通讯作者：
Ussher, John R.
中科院分区：
文献类型：
--
作者：
Eshreif, Amina;Al Batran, Rami;Ussher, John R.
新发现研究的中心问题是什么？瓜氨酸的作用已被证明可以提高动物和运动员的表现，可能是通过增加线粒体功能，是否会转化为肥胖动物，这是否会改善贫血？主要发现及其重要性是什么？长期补充L-瓜氨酸不仅可以改善肥胖小鼠的运动能力，还可以改善肥胖小鼠的高血糖症，这将是有益的，因为肥胖个体患2型糖尿病的风险增加。然而，补充l-瓜氨酸也会导致肥胖小鼠的胰岛素信号传导和胰岛素耐受性轻度受损。L-瓜氨酸是一种有机α-氨基酸，已被证明对全身生理学具有许多有益作用，包括减少肌肉消耗和增强运动和肌肉性能。后者被认为是由线粒体功能的升高引起的。由于增强线粒体功能已被提出作为减轻胰岛素抵抗的新策略，我们的目标是确定补充l-瓜氨酸是否也可以改善实验性肥胖小鼠模型中的高血糖症。我们假设L-瓜氨酸治疗可以改善肥胖小鼠的高血糖症，这与骨骼肌线粒体功能的提高有关。给10周龄的C57 BL/6J小鼠喂食低脂（10%千卡来自猪油）或高脂（60%千卡来自猪油）饮食，同时饮用补充有溶剂或l-瓜氨酸（0.6 g l（-1））的饮用水，持续15周。通过葡萄糖/胰岛素耐量试验评估葡萄糖稳态，而通过间接热量测定法评估体内代谢，并利用强迫运动跑步机试验评估耐力。正如预期的那样，补充l-瓜氨酸的肥胖小鼠表现出运动能力的增加，这与葡萄糖耐量的改善有关。与线粒体功能增强一致，我们观察到补充l-瓜氨酸的肥胖小鼠全身耗氧率增加。令人惊讶的是，l-瓜氨酸补充剂恶化了肥胖小鼠的胰岛素耐受性并减少了胰岛素信号传导。综上所述，虽然补充L-瓜氨酸可以改善肥胖小鼠的葡萄糖耐量和运动能力，但由于其可能会降低胰岛素敏感性，因此必须谨慎使用其作为营养药物。
New FindingsWhat is the central question of the study?Does the action of l-citrulline, which has been shown to augment performance in animals and athletes, possibly via increasing mitochondrial function, translate to obese animals, and does this improve glycaemia? What is the main finding and its importance?Chronic supplementation with l-citrulline improves not only exercise capacity, but also glycaemia in obese mice, which would be beneficial as obese individuals are at increased risk for type 2 diabetes. However, l-citrulline supplementation also caused a mild impairment in insulin signalling and insulin tolerance in obese mice. l-Citrulline is an organic alpha-amino acid that has been shown to have a number of salutary actions on whole-body physiology, including reducing muscle wasting and augmenting exercise and muscle performance. The latter has been suggested to arise from elevations in mitochondrial function. Because enhancing mitochondrial function has been proposed as a novel strategy to mitigate insulin resistance, our goal was to determine whether supplementation with l-citrulline could also improve glycaemia in an experimental mouse model of obesity. We hypothesized that l-citrulline treatment would improve glycaemia in obese mice, and this would be associated with elevations in skeletal muscle mitochondrial function. Ten-week-old C57BL/6J mice were fed either a low-fat (10% kcal from lard) or a high-fat (60% kcal from lard) diet, while receiving drinking water supplemented with either vehicle or l-citrulline (0.6 g l(-1)) for 15 weeks. Glucose homeostasis was assessed via glucose/insulin tolerance testing, while in vivo metabolism was assessed via indirect calorimetry, and forced exercise treadmill testing was utilized to assess endurance. As expected, obese mice supplemented with l-citrulline exhibited an increase in exercise capacity, which was associated with an improvement in glucose tolerance. Consistent with augmented mitochondrial function, we observed an increase in whole body oxygen consumption rates in obese mice supplemented with l-citrulline. Surprisingly, l-citrulline supplementation worsened insulin tolerance and reduced insulin signalling in obese mice. Taken together, although l-citrulline supplementation improves both glucose tolerance and exercise capacity in obese mice, caution must be applied with its broad use as a nutraceutical due to a potential deterioration of insulin sensitivity.