Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia
Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia
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DOI：
10.1210/en.2007-0016
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发表时间：
2007-06-01
期刊：
影响因子：
4.8
通讯作者：
Marks, Daniel L.
中科院分区：
文献类型：
--
作者：
DeBoer, Mark D.;Zhu, Xin Xia;Marks, Daniel L.
癌症恶病质是一种伴随许多恶性肿瘤的厌食和瘦体重减少的衰弱综合征。生长激素释放肽是一种具有短半衰期的促食欲激素，已显示其在患有癌症恶病质的人类和动物受试者中改善食物摄入和体重增加。我们使用大鼠癌症恶病质模型，并通过皮下渗透微型泵连续输注给予人生长素释放肽和合成生长素释放肽类似物BIM-28131。与盐水处理的动物相比，接受人生长素释放肽或BIM-28131的肿瘤植入大鼠表现出食物消耗和体重增加的显著增加。我们使用双能X射线吸收测量扫描显示，体重增加是由于维持瘦体重而不是盐水处理动物的瘦体重损失。此外，BIM-28131显著限制了通常在肿瘤植入大鼠中观察到的脂肪量损失。我们进一步对下丘脑和脑干进行了实时PCR分析，发现Ghrelin治疗的动物下丘脑中食欲肽、刺豚鼠相关肽和神经肽Y的表达显著增加，下丘脑和脑干中IL-1受体-I转录物的表达显著减少。我们得出结论，生长激素释放肽和合成生长激素释放肽受体激动剂通过影响食欲神经肽和食欲的变化，改善体重增加和瘦体重保持。
Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes.