Cachexia in MAC16 adenocarcinoma: Suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y
Cachexia in MAC16 adenocarcinoma: Suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y
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DOI：
10.1046/j.1471-4159.2001.00639.x
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发表时间：
2001-12-01
影响因子：
4.7
通讯作者：
Williams, G
中科院分区：
文献类型：
--
作者：
Bing, C;Taylor, S;Williams, G
体重减轻通常会刺激饥饿感，其机制包括循环中瘦素和胰岛素的福尔斯下降，导致下丘脑神经肽Y（NPY）的刺激。在这里，我们研究了瘦素，胰岛素和神经肽Y，以澄清为什么饥饿是由MAC 16腺癌引起的严重恶病质小鼠的抑制。携带MAC 16的小鼠在肿瘤移植后16天内逐渐减轻体重（比对照组低19%）和脂肪（-61%），而总食物摄入量下降了10%。配对喂养的小鼠表现出更少的浪费，最终体重为9%，脂肪量比对照组低25%。血浆瘦素下降了85%，在MAC 16和51%的配对喂养的小鼠，成比例的脂肪损失。血浆胰岛素在MAC 16中也降低了49%，在成对喂养组中降低了53%。MAC 16（+223%）和配对喂养（+192%）小鼠的下丘脑瘦素受体（OB-Rb）mRNA均显著增加。下丘脑NPY mRNA在MAC 16组（+152%）和配对喂养组（+99%）也显著升高，与血浆瘦素和胰岛素呈负相关，与OB-Rb mRNA呈正相关。在MAC 16诱导的恶病质中，瘦素产生和下丘脑OB-Rb和NPY表达响应于脂肪消耗而适当调节。因此，饥饿的抑制可能是由于肿瘤产物抑制NPY的转运或释放，或干扰NPY下游的神经元靶点。
Weight loss normally stimulates hunger, through mechanisms that include falls in circulating leptin and insulin, leading to stimulation of hypothalamic neuropeptide Y (NPY). Here, we investigated the leptin, insulin and NPY to clarify why hunger is suppressed in mice with severe cachexia due to the MAC16 adenocarcinoma. MAC16-bearing mice progressively lost weight (19% below controls) and fat (-61%) over 16 days after tumour transplantation, while total food intake fell by 10%. Pair-fed mice showed less wasting, with final weight being 9% and fat mass 25% below controls. Plasma leptin fell by 85% in MAC16 and 51% in pair-fed mice, in proportion to loss of fat. Plasma insulin was also reduced by 49% in MAC16 and 53% in pair-fed groups. Hypothalamic leptin receptor (OB-Rb) mRNA was significantly increased in both MAC16 (+223 %) and pair-fed (+192 %) mice. Hypothalamic NPY mRNA was also significantly raised in MAC16 (+152 %) and pair-fed (+99 %) groups, showing negative correlations with plasma leptin and insulin, and a positive association with OB-Rb mRNA. In MAC16-induced cachexia, leptin production and hypothalamic OB-Rb and NPY expression are regulated appropriately in response to fat depletion. Therefore, suppression of hunger is probably due to tumour products that inhibit NPY transport or release, or that interfere with neuronal targets downstream of NPY.