l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents.
l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents.
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DOI：
10.1038/ijo.2017.164
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Murphy KG
中科院分区：
文献类型：
--
作者：
Alamshah A;Spreckley E;Norton M;Kinsey-Jones JS;Amin A;Ramgulam A;Cao Y;Johnson R;Saleh K;Akalestou E;Malik Z;Gonzalez-Abuin N;Jomard A;Amarsi R;Moolla A;Sargent PR;Gray GW;Bloom SR;Murphy KG
高蛋白饮食（HPD）与富含其他大量营养素的饮食相比，具有更大的饱腹感和体重减轻。HPD发挥其作用的确切机制尚不清楚。然而，有证据表明，由于蛋白质消化而产生的氨基酸的传感可能在食欲调节和饱腹感中起作用。本文研究了L-苯丙氨酸（L-Phe）对啮齿类动物摄食量和葡萄糖稳态的影响。我们研究了芳香族氨基酸和钙敏感受体（CaSR）激动剂L-苯丙氨酸（L-Phe）对啮齿动物摄食和胃肠道（GI）激素肽YY（PYY），胰高血糖素样肽-1（GLP-1）和ghrelin释放的影响，以及CaSR在体外和体内介导这些效应中的作用。我们还研究了口服L-Phe给药对大鼠葡萄糖耐量的影响。口服l-Phe急性减少大鼠和小鼠的食物摄入量，慢性减少饮食诱导的肥胖小鼠的食物摄入量和体重。回肠l-Phe还减少大鼠的食物摄入。L-Phe刺激GLP-1和PYY释放，降低血浆ghrelin，还刺激胰岛素释放，改善大鼠的糖耐量。CaSR的药理学阻断减弱了大鼠回肠内l-Phe的厌食作用，并且通过CaSR阻断减弱了l-Phe诱导的STC-1和原代L细胞的GLP-1释放。在啮齿动物中，l-Phe减少食物摄入，刺激GLP-1和PYY释放，并减少血浆ghrelin。我们的数据提供了证据表明，l-Phe的厌食作用是通过CaSR介导的，并表明，在胃肠道中的l-Phe和CaSR系统可能在治疗肥胖症和糖尿病的治疗效用。需要进一步的工作来确定CaSR在肠道蛋白质传感中的生理作用，以及该系统在人类中的作用。
High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo. We also examined the effect of oral l-Phe administration on glucose tolerance in rats. Oral administration of l-Phe acutely reduced food intake in rats and mice, and chronically reduced food intake and body weight in diet-induced obese mice. Ileal l-Phe also reduced food intake in rats. l-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and also stimulated insulin release and improved glucose tolerance in rats. Pharmacological blockade of the CaSR attenuated the anorectic effect of intra-ileal l-Phe in rats, and l-Phe-induced GLP-1 release from STC-1 and primary L cells was attenuated by CaSR blockade. l-Phe reduced food intake, stimulated GLP-1 and PYY release, and reduced plasma ghrelin in rodents. Our data provide evidence that the anorectic effects of l-Phe are mediated via the CaSR, and suggest that l-Phe and the CaSR system in the GI tract may have therapeutic utility in the treatment of obesity and diabetes. Further work is required to determine the physiological role of the CaSR in protein sensing in the gut, and the role of this system in humans.
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影响因子：
5.5
作者：
Jordi, Josua;Herzog, Brigitte;Verrey, Francois
通讯作者：
Verrey, Francois
影响因子：
4.2
作者：
BIALIK, RJ;LI, ETS;ANDERSON, GH
通讯作者：
ANDERSON, GH
DOI：
10.3945/ajcn.2008.26362
发表时间：
2009-01
期刊：
The American journal of clinical nutrition
影响因子：
--
作者：
Greenfield JR;Farooqi IS;Keogh JM;Henning E;Habib AM;Blackwood A;Reimann F;Holst JJ;Gribble FM
通讯作者：
Gribble FM
影响因子：
2.1
作者：
CHO, CY;BAYLEY, HS
通讯作者：
BAYLEY, HS
影响因子：
5.4
作者：
Hira, Tohru;Nakajima, Shingo;Hara, Hiroshi
通讯作者：
Hara, Hiroshi