Functional implications of limited leptin receptor and ghrelin receptor coexpression in the brain.
Functional implications of limited leptin receptor and ghrelin receptor coexpression in the brain.
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DOI：
10.1002/cne.22690
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发表时间：
2012-02-01
影响因子：
2.5
通讯作者：
Zigman, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Perello, Mario;Scott, Michael M.;Sakata, Ichiro;Lee, Charlotte E.;Chuang, Jen-Chieh;Osborne-Lawrence, Sherri;Rovinsky, Sherry A.;Elmquist, Joel K.;Zigman, Jeffrey M.
激素瘦素和生长激素释放肽在体重稳态的调节中彼此并置起作用。有趣的是，在中枢神经系统（CNS）的许多相同核团中观察到瘦素受体表达和饥饿素受体表达，这表明这些激素可能作用于常见的神经元群体，从而产生食物摄入和能量消耗的变化。在本研究中，我们探讨了这种假定的直接瘦素和生长激素释放肽在中枢神经系统中的相互作用的程度，并解决了生长激素释放肽信号转导的损失是否会影响对瘦素的敏感性的问题。利用瘦素受体和生长激素释放肽受体表达的组织学定位，我们发现含有瘦素受体和生长激素释放肽受体的细胞主要位于下丘脑弓状核的内侧部分。相比之下，共表达在大脑其他地方的范围要小得多。为了评估所观察到的受体分布的功能后果，我们探讨了生长激素释放肽受体缺失对瘦素敏感性的影响。特别是，随意喂养，饮食诱导的肥胖和禁食小鼠瘦素的厌食作用的反应进行了检查。令人惊讶的是，我们发现生长激素释放肽受体的缺失并不影响对外源性瘦素的敏感性。因此，我们得出结论，生长激素释放肽和瘦素主要作用于不同的神经元群体，生长激素释放肽受体缺乏并不影响瘦素的促生长和体重减轻作用的敏感性。
The hormones leptin and ghrelin act in apposition to one another in the regulation of body weight homeostasis. Interestingly, both leptin receptor expression and ghrelin receptor expression have been observed within many of the same nuclei of the central nervous system (CNS), suggesting that these hormones may act on a common population of neurons to produce changes in food intake and energy expenditure. In the present study we explored the extent of this putative direct leptin and ghrelin interaction in the CNS and addressed the question of whether a loss of ghrelin signaling would affect sensitivity to leptin. Using histological mapping of leptin receptor and ghrelin receptor expression, we found that cells containing both leptin receptors and ghrelin receptors are mainly located in the medial part of the hypothalamic arcuate nucleus. In contrast, coexpression was much less extensive elsewhere in the brain. To assess the functional consequences of this observed receptor distribution, we explored the effect of ghrelin receptor deletion on leptin sensitivity. In particular, the responses of ad libitum-fed, diet-induced obese and fasted mice to the anorectic actions of leptin were examined. Surprisingly, we found that deletion of the ghrelin receptor did not affect the sensitivity to exogenously administrated leptin. Thus, we conclude that ghrelin and leptin act largely on distinct neuronal populations and that ghrelin receptor deficiency does not affect sensitivity to the anorexigenic and body weight-lowering actions of leptin.
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影响因子：
16.2
作者：
Elias, CF;Aschkenasi, C;Elmquist, JK
通讯作者：
Elmquist, JK
影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
影响因子：
16.2
作者：
Cowley, MA;Smith, RG;Horvath, TL
通讯作者：
Horvath, TL
影响因子：
15.9
作者：
Abizaid, Alfonso;Liu, Zhong-Wu;Horvath, Tamas L.
通讯作者：
Horvath, Tamas L.
影响因子：
2.5
作者：
Elmquist, JK;Coppari, R;Lowell, BB
通讯作者：
Lowell, BB