Adelaide Medical School and Center of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Adelaide Medical School and Center of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
Am J Clin Nutr. 2024 Sep;120(3):528-539. doi: 10.1016/j.ajcnut.2024.07.006. Epub 2024 Jul 10.
In humans, intraduodenal infusion of L-tryptophan (Trp) increases plasma concentrations of gastrointestinal hormones and stimulates pyloric pressures, both key determinants of gastric emptying and associated with potent suppression of energy intake. The stimulation of gastrointestinal hormones by Trp has been shown, in preclinical studies, to be enhanced by extracellular calcium and mediated in part by the calcium-sensing receptor.
This study aim was to determine whether intraduodenal calcium can enhance the effects of Trp to stimulate gastrointestinal hormones and pyloric pressures and, if so, whether it is associated with greater suppression of energy intake, in healthy males.
Fifteen males with normal weight (mean ± standard deviation; age: 26 ± 7 years; body mass index: 22 ± 2 kg/m), received on 3 separate occasions, 150-min intraduodenal infusions of 0, 500, or 1000 mg calcium (Ca), each combined with Trp (load: 0.1 kcal/min, with submaximal energy intake-suppressant effects) from t = 75-150 min, in a randomized, double-blind, crossover study. Plasma concentrations of GI hormones [gastrin, cholecystokinin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide (GLP)-1, and peptide tyrosine-tyrosine (PYY)], and Trp and antropyloroduodenal pressures were measured throughout. Immediately postinfusions (t = 150-180 min), energy intake at a standardized buffet-style meal was quantified.
In response to calcium alone, both 500- and 1000-mg doses stimulated PYY, while only the 1000-mg dose stimulated GLP-1 and pyloric pressures (all P < 0.05). The 1000-mg dose also enhanced the effects of Trp to stimulate cholecystokinin and GLP-1, and both doses stimulated PYY but, surprisingly, reduced the stimulation of GIP (all P < 0.05). Both doses substantially and dose dependently enhanced the effects of Trp to suppress energy intake (Ca-0+Trp: 1108 ± 70 kcal; Ca-500+Trp: 961 ± 90 kcal; and Ca-1000+Trp: 922 ± 96 kcal; P < 0.05).
Intraduodenal administration of calcium enhances the effect of Trp to stimulate plasma cholecystokinin, GLP-1, and PYY and suppress energy intake in healthy males. These findings have potential implications for novel nutrient-based approaches to energy intake regulation in obesity. The trial was registered at the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12620001294943).
在人类中，十二指肠内输注 L-色氨酸（Trp）会增加胃肠激素的血浆浓度，并刺激幽门压力，这两者都是胃排空的关键决定因素，与能量摄入的强烈抑制有关。在临床前研究中，已经表明色氨酸对胃肠激素的刺激作用会被细胞外钙增强，并部分通过钙敏感受体介导。
本研究旨在确定十二指肠内钙是否可以增强色氨酸刺激胃肠激素和幽门压力的作用，如果可以，它是否与健康男性的能量摄入抑制程度更大有关。
15 名体重正常的男性（平均值±标准差；年龄：26±7 岁；体重指数：22±2kg/m），在 3 次单独的情况下，分别接受 0、500 或 1000mg 钙（Ca）的 150 分钟十二指肠内输注，同时在 t=75-150 分钟内输注 Trp（负荷：0.1kcal/min，具有亚最大能量摄入抑制作用），在一项随机、双盲、交叉研究中。整个过程中测量胃肠激素[胃泌素、胆囊收缩素、葡萄糖依赖性胰岛素释放肽（GIP）、胰高血糖素样肽（GLP）-1 和肽酪氨酸酪氨酸（PYY）]和色氨酸的浓度和幽门十二指肠压力。输注后立即（t=150-180min），在标准化的自助式餐中定量摄入的能量。
单独给予钙时，500mg 和 1000mg 剂量均可刺激 PYY，而只有 1000mg 剂量可刺激 GLP-1 和幽门压力（均 P<0.05）。1000mg 剂量还增强了 Trp 刺激胆囊收缩素和 GLP-1 的作用，两种剂量均刺激 PYY，但令人惊讶的是，降低了 GIP 的刺激作用（均 P<0.05）。两种剂量均显著且剂量依赖性地增强了 Trp 抑制能量摄入的作用（Ca-0+Trp：1108±70kcal；Ca-500+Trp：961±90kcal；Ca-1000+Trp：922±96kcal；P<0.05）。
十二指肠内给予钙可增强色氨酸刺激血浆胆囊收缩素、GLP-1 和 PYY 的作用，并抑制健康男性的能量摄入。这些发现可能对肥胖症中基于营养素的能量摄入调节的新方法具有重要意义。该试验在澳大利亚和新西兰临床试验注册中心（www.anzctr.org.au）注册，注册号为 ACTRN12620001294943。
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