Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular (CIMUS), Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain.
Cells. 2022 Jan 19;11(3):324. doi: 10.3390/cells11030324.
Data gleaned recently shows that ghrelin, a stomach derived peptide, and liver-expressed-antimicrobial peptide 2 (LEAP-2) play opposite roles on food intake. However, the data available with LEAP-2 in relation to in vivo studies are still very scanty and some key questions regarding the interplay among ghrelin and LEAP-2 remain to be answered. In this work, using rats and mice, we study fasting-induced food intake as well as testing the effect of diet exposure, e.g., standard diet and high fat diet, in terms of ghrelin-induced food intake. The anorexigenic effect of LEAP-2 on fasting induced food intake appears to be dependent on energy stores, being more evident in than in wild type mice and also in animals exposed to high fat diet. On the other hand, LEAP-2 administration markedly inhibited ghrelin-induced food intake in lean, obese ( and DIO) mice, aged rats and GH-deficient dwarf rats. In contrast, the inhibitory effect on glucose levels can only be observed in some specific experimental models indicating that the mechanisms involved are likely to be quite different. Taken together from these data, LEAP-2 emerged as a potential candidate to be therapeutically useful in obesity.
最近获得的数据表明，胃来源肽 ghrelin 和肝表达抗菌肽 2（LEAP-2）在摄食方面发挥着相反的作用。然而，关于 LEAP-2 的体内研究数据仍然非常有限，关于 ghrelin 和 LEAP-2 之间相互作用的一些关键问题仍有待回答。在这项工作中，我们使用大鼠和小鼠研究了禁食诱导的食物摄入，并测试了饮食暴露（例如标准饮食和高脂肪饮食）对 ghrelin 诱导的食物摄入的影响。LEAP-2 对禁食诱导的食物摄入的厌食作用似乎依赖于能量储存，在 小鼠中比在野生型小鼠中更为明显，并且在暴露于高脂肪饮食的动物中也更为明显。另一方面，LEAP-2 给药在瘦、肥胖（和 DIO）小鼠、老年大鼠和 GH 缺乏性 dwarf 大鼠中显著抑制了 ghrelin 诱导的食物摄入。相比之下，在一些特定的实验模型中只能观察到对葡萄糖水平的抑制作用，这表明所涉及的机制可能非常不同。从这些数据综合来看，LEAP-2 作为一种有治疗肥胖潜力的候选药物。
