Stark Romana, Reichenbach Alex, Lockie Sarah H, Pracht Corinna, Wu Qunli, Tups Alexander, Andrews Zane B
Department of Physiology (R.S., A.R., S.H.L., Q.W., Z.B.A.), Monash University, Clayton, Victoria 3800, Australia; Traditional Chinese Medicine Department (Q.W.), Peking Union Medical College Hospital, Dongcheng District, Beijing 100730, China; Department of Animal Physiology (C.P., A.T.), Faculty of Biology, Phillips University, D-35043 Marburg, Germany; and Department of Physiology (A.T.), Otago School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand.
Endocrinology. 2015 Mar;156(3):858-68. doi: 10.1210/en.2014-1733. Epub 2014 Dec 23.
Recent evidence suggests that peripheral ghrelin regulates glucose metabolism. Here, we designed experiments to examine how central acyl ghrelin infusion affects peripheral glucose metabolism under pair-fed or ad libitum feeding conditions. Mice received intracerebroventricular (icv) infusion of artificial cerebrospinal fluid (aCSF), ghrelin, and allowed to eat ad libitum (icv ghrelin ad lib) or ghrelin and pair-fed to the aCSF group (icv ghrelin pf). Minipumps delivered acyl ghrelin at a dose of 0.25 μg/h at 0.5 μL/h for 7 days. There was no difference in daily blood glucose, insulin, glucagon, triglycerides, or nonesterified fatty acids. Body weight gain and food intake was significantly higher in icv ghrelin ad lib mice. However, both icv ghrelin ad lib and icv ghrelin pf groups exhibited heavier white adipose mass. Icv ghrelin pf mice exhibited better glucose tolerance than aCSF or icv ghrelin ad lib mice during a glucose tolerance test, although both icv ghrelin ad lib and icv ghrelin pf increased insulin release during the glucose tolerance test. Central acyl ghrelin infusion and pair feeding also increased breakdown of liver glycogen and triglyceride, and regulated genes involved in hepatic lipid and glucose metabolism. Icv ghrelin pf mice had an increase in plasma blood glucose during a pyruvate tolerance test relative to icv ghrelin ad lib or aCSF mice. Our results suggest that under conditions of negative energy (icv ghrelin pf), central acyl ghrelin engages a neural circuit that influences hepatic glucose function. Metabolic status affects the ability of central acyl ghrelin to regulate peripheral glucose homeostasis.
近期证据表明，外周胃饥饿素可调节葡萄糖代谢。在此，我们设计了实验，以研究在成对喂养或自由进食条件下，脑室内注入酰基胃饥饿素如何影响外周葡萄糖代谢。小鼠接受脑室内（icv）注入人工脑脊液（aCSF）、胃饥饿素，并允许自由进食（icv胃饥饿素自由进食组）或注入胃饥饿素并与aCSF组成对喂养（icv胃饥饿素成对喂养组）。微型泵以0.5 μL/h的速度以0.25 μg/h的剂量输送酰基胃饥饿素，持续7天。每日血糖、胰岛素、胰高血糖素、甘油三酯或非酯化脂肪酸无差异。icv胃饥饿素自由进食组小鼠的体重增加和食物摄入量显著更高。然而，icv胃饥饿素自由进食组和icv胃饥饿素成对喂养组的白色脂肪量均较重。在葡萄糖耐量试验中，icv胃饥饿素成对喂养组小鼠的葡萄糖耐量优于aCSF组或icv胃饥饿素自由进食组小鼠，尽管icv胃饥饿素自由进食组和icv胃饥饿素成对喂养组在葡萄糖耐量试验期间均增加了胰岛素释放。脑室内注入酰基胃饥饿素和成对喂养还增加了肝糖原和甘油三酯的分解，并调节了参与肝脏脂质和葡萄糖代谢的基因。相对于icv胃饥饿素自由进食组或aCSF组小鼠，icv胃饥饿素成对喂养组小鼠在丙酮酸耐量试验期间血浆血糖升高。我们的结果表明，在负能量（icv胃饥饿素成对喂养组）条件下，中枢酰基胃饥饿素激活了一条影响肝脏葡萄糖功能的神经回路。代谢状态影响中枢酰基胃饥饿素调节外周葡萄糖稳态的能力。
