Energy Homeostasis and gastric emptying in ghrelin knockout mice
Energy Homeostasis and gastric emptying in ghrelin knockout mice
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DOI：
10.1124/jpet.105.091504
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Peeters, TL
中科院分区：
文献类型：
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作者：
De Smet, B;Depoortere, I;Peeters, TL
为了阐明内源性生长素释放肽在能量稳态和胃排空调节中的作用，产生了生长素释放肽敲除小鼠（生长素释放肽（-/-））。比较 ghrelin(+/+) 和 ghrelin(-/-) 小鼠的体重、食物摄入量、呼吸商、产热（间接量热法）和胃排空（C-14 呼吸测试）。在这两种菌株中，确定了外源性生长素释放肽对胃排空和食物摄入的影响。 Ghrelin(-/-) 小鼠表现出一些微妙的表型变化。体重增加和 24 小时食物摄入量没有受到影响，但正常光/暗周期的中断会引发老年 ghrelin(+/+) 小鼠的额外食物摄入量，但 ghrelin (-/-) 小鼠则不会。外源性生长素释放肽增加了两种基因型的食物摄入量，并且在生长素释放肽(-/-)小鼠中呈钟形剂量反应曲线向左移动。在黑暗时期，年轻的ghrelin(-/-)小鼠的呼吸商较低，而它们的产热量高于野生型同窝小鼠，这表明ghrelin(-/-)小鼠的身体成分更瘦。缺乏生长素释放肽并不影响胃排空，并且外源性生长素释放肽加速胃排空的钟形剂量反应曲线在两种菌株之间没有变化。总之，生长素释放肽并不是食物摄入和胃排空的重要调节剂，但其损失可以通过其他多余的输入来补偿。在老年小鼠中，由光/暗提示触发的进餐可能与生长素释放肽有关。在幼年动物中，生长素释放肽似乎参与能量储存的选择以及代谢能量在储存和以热量形式耗散之间的分配。
To elucidate the role of endogenous ghrelin in the regulation of energy homeostasis and gastric emptying, ghrelin knockout mice ( ghrelin(-/-)) were generated. Body weight, food intake, respiratory quotient, and heat production ( indirect calorimetry), and gastric emptying ( C-14 breath test) were compared between ghrelin(+/+) and ghrelin(-/-) mice. In both strains, the effect of exogenous ghrelin on gastric emptying and food intake was determined. Ghrelin(-/-) mice showed some subtle phenotypic changes. Body weight gain and 24-h food intake were not affected, but interruption of the normal light/dark cycle triggered additional food intake in old ghrelin(+/+) but not in ghrelin (-/-) mice. Exogenous ghrelin increased food intake in both genotypes with a bell-shaped dose-response curve that was shifted to the left in ghrelin(-/-) mice. During the dark period, young ghrelin(-/-) mice had a lower respiratory quotient, whereas their heat production was higher than that of the wild-type littermates, inferring a leaner body composition of the ghrelin(-/-) mice. Absence of ghrelin did not affect gastric emptying, and the bell- shaped dose-response curves of the acceleration of gastric emptying by exogenous ghrelin were not shifted between both strains. In conclusion, ghrelin is not an essential regulator of food intake and gastric emptying, but its loss may be compensated by other redundant inputs. In old mice, meal initiation triggered by the light/dark cue may be related to ghrelin. In young animals, ghrelin seems to be involved in the selection of energy stores and in the partitioning of metabolizable energy between storage and dissipation as heat.