Induced ablation of ghrelin cells in adult mice does not decrease food intake, body weight, or response to high-fat diet.
Induced ablation of ghrelin cells in adult mice does not decrease food intake, body weight, or response to high-fat diet.
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DOI：
10.1016/j.cmet.2014.04.007
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发表时间：
2014-07-01
期刊：
影响因子：
29
通讯作者：
Zhao TJ
中科院分区：
文献类型：
--
作者：
McFarlane MR;Brown MS;Goldstein JL;Zhao TJ
注射肽激素生长激素释放肽刺激小鼠和人类的食物摄入。然而，出生时没有生长激素释放肽的小鼠没有表现出明显的食欲不振。这种矛盾的现象表明，要么是在出生时没有生长激素释放肽的小鼠中产生了补偿，要么是生长激素释放肽对食欲控制并不重要。为了区分这些可能性，我们产生了在ghrelin分泌细胞中表达白喉毒素受体的转基因小鼠（Ghrl-DTR）。在成年期注射白喉毒素可消融生长素释放肽细胞，并使血浆生长素释放肽减少80- 95%。Ghrelin细胞消融的小鼠没有表现出食欲或体重下降，对高脂肪饮食没有抵抗力。为了通过注射生长激素释放肽刺激小鼠的食物摄入，我们不得不将血浆水平提高到正常水平的许多倍。与种系生长素释放肽缺陷小鼠一样，生长素释放肽细胞消融小鼠在长时间限制热量时发生严重的低血糖，证实了生长素释放肽在饥饿条件下维持血糖的作用。
Injection of the peptide hormone ghrelin stimulates food intake in mice and humans. However, mice born without ghrelin demonstrate no significant loss of appetite. This paradox suggests either that compensation develops in mice born without ghrelin or that ghrelin is not essential for appetite control. To distinguish these possibilities, we generated transgenic mice (Ghrl-DTR) that express the diphtheria toxin receptor in ghrelin-secreting cells. Injection of diphtheria toxin in adulthood ablated ghrelin cells and reduced plasma ghrelin by 80-95%. Ghrelin cell-ablated mice exhibited no loss of appetite or body weight and no resistance to a high fat diet. To stimulate food intake in mice by ghrelin injection, we had to raise plasma levels many-fold above normal. Like germline ghrelin-deficient mice, the ghrelin cell-ablated mice developed profound hypoglycemia when subjected to prolonged calorie restriction, confirming that ghrelin acts to maintain blood glucose under famine conditions.
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