Inputs and outputs of NPY and BDNF neurons in the hypothalamus and their implication in feeding and metabolic regulation

我们分析了神经肽Y （NPY）神经元和脑源性神经营养因子（BDNF）神经元的输入和输出。下丘脑弓状核（ARC）的NPY神经元被胃饥饿素激活，被瘦素抑制。瘦素通过PI3激酶和PDE3信号通路，在NPY神经元中抵消ghrelin的作用。两种激素的结合决定了NPY神经元的活动和摄食行为。2型糖尿病模型GK大鼠表现为青壮年特异性贪食，这是由ARC中NPY mRNA表达升高引起的，提示ARC NPY神经元的病理生理作用。中枢注射BDNF增加室旁核（PVN）促肾上腺皮质激素释放激素（CRH）和尿皮质素的表达，从而抑制摄食并通过CRH- r2受体增加能量消耗。一种新的厌食肽nesfatin-1在PVN中大量存在并与CRH共定位，提示nesfatin-1可能作为BDNF-CRH系统的调节因子。

We analyzed the inputs and outputs of neuropeptide Y (NPY) neurons and brain-derived neurotrophic factor (BDNF) neurons. NPY neurons in the hypothalamic arcuate : nucleus (ARC) were activated by ghrelin and inhibited by leptin. Leptin, via PI3 kinase and PDE3 signaling pathway, counteracted the action of ghrelin in NPY neurons. The integration of the two hormones determined the activity of NPY neurons and the feeding behavior. GK rats, a model of type 2 diabetes, showed young-adult specific hyperphagia, which was caused by elevated expression of NPY mRNA in the ARC, suggesting the pathophysiological role of the ARC NPY neurons.Central injection of BDNF increased expression of corticotropin-releasing hormone (CRH) and urocortin in the paraventricular nucleus (PVN), and thereby inhibited feeding and enhanced energy expenditure via CRH-R2 receptors. A new anorectic peptide, nesfatin-1, was abundant in PVN and colocalized with CRH, suggesting that nesfatin-1 could serve as a regulator of BDNF-CRH system.