Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
J Comp Neurol. 2012 Feb 1;520(2):281-94. doi: 10.1002/cne.22690.
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.
瘦素和胃饥饿素在调节体重平衡方面相互作用。有趣的是，瘦素受体表达和胃饥饿素受体表达都在中枢神经系统（CNS）的许多相同核中观察到，这表明这些激素可能作用于共同的神经元群体，以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瘦素和胃饥饿素在中枢神经系统中的直接相互作用的程度，并解决了胃饥饿素信号缺失是否会影响对瘦素的敏感性的问题。使用瘦素受体和胃饥饿素受体表达的组织学映射，我们发现含有瘦素受体和胃饥饿素受体的细胞主要位于下丘脑弓状核的中间部分。相比之下，在大脑的其他部位，共表达的程度要小得多。为了评估这种观察到的受体分布的功能后果，我们探讨了胃饥饿素受体缺失对瘦素敏感性的影响。特别是，检查了自由喂养、饮食诱导肥胖和禁食小鼠对瘦素厌食作用的反应。令人惊讶的是，我们发现胃饥饿素受体缺失并不影响对外源给予的瘦素的敏感性。因此，我们得出结论，胃饥饿素和瘦素主要作用于不同的神经元群体，而胃饥饿素受体缺乏并不影响对瘦素的厌食和降低体重作用的敏感性。
