由肠腔内容物引起的GLP-1的释放可减慢胃排空和小肠运动，参与所谓“回肠制动”效应。GLP-1能抑制餐后胃排空和减少胃酸分泌，可通过抑制迷走神经而抑制胃和十二指肠的蠕动，增加幽门部的压力，从而延缓胃排空，降低食欲，减轻体重。给正常个体静脉注射GLP-1可使50％胃排空时间由(28±2)min延长到(50±9)min[30]。
瘦素的中枢作用通过其对下丘脑神经肽通路的影响而实现。瘦素受体在弓状核，腹侧正中下丘脑核、边下丘脑核、背中线下丘脑核、旁室旁核都有高水平表达。下丘脑的神经肽(NPY)是促进摄食量的一个最强有力的诱导因子和棕色脂肪组织产热的抑制因子，它能增加血中胰岛素水平。体重增加使脂肪组织表达其自身容积的信号-瘦素分泌增加。作用于下丘脑使POMC系统合成增加，MSH为其一种成份，作用于黑色素促皮质受体4(M4)，引起摄食减少，耗能增加及交感神经功能加强以消耗脂肪的容量。而当机体处于饥饿状态脂肪组织容量的下降时，瘦素作用于下丘脑使NPY合成分泌增加，通过Y5受体，机体产生摄食增加，副交感功能增强，耗能减少，从而恢复脂肪的容量。在许多肥胖鼠和禁食鼠模型中，下丘脑NPY的表达上升，通过瘦素处理可以直接抑制NPY从正常动物下丘脑的释放，引起采食量迅速降低，产热增加及在体重降低之前的糖血症及胰岛素血症的改善。在饥饿状况下，NPY神经元被激发，大部分是由于NPY的激发降低了用来抑制NPY激发的瘦素水平；反之，瘦素则抑制NPY的激发。因此，在脑和神经下行作用时，NPY是瘦素作用的主要目标。当瘦素不起中枢作用时，NPY水平不断提高，因此出现肥胖；当下丘脑NPY和瘦素共同作用时，体重表现出自身的稳定性。NPY遗传缺失的小鼠仍能维持正常体重，说明了瘦素还有可能通过其它一些因子和途径来调节体重[31]。
在脑干的GLP-1的神经元发现有瘦素受体，暗示着二者有相互作用。瘦素可以加强GLP-1的对食物摄取和体重减少的作用，因为都可以诱导转录因子c-fos的表达，也可能激活与摄食有关的神经元活性。干扰GLP–1信号不会影响的ob/ob小鼠的长期控制体重或胰岛素抵抗的作用。GLP-1和低剂量的瘦素对摄食的抑制作用相加。同时在结节神经节细胞发现他们的受体，瘦素和GLP-1在外周也是相互作用，瘦素可以刺激GLP-1的释放。在急性试验中低剂量的瘦素不改变GLP-1依赖的食物摄取。相似的，重复注射瘦素不影响GLP-1诱导的摄食抑制。GLP-1为影响食欲的短期信号，即仅影响到一顿饭的食欲，而瘦素是影响食欲的长期信号，决定食欲的基础水平[32]。

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