PDF(Pubmed)
Abstract：
Glucoprivic feeding is one of several counterregulatory responses (CRRs) that facilitates restoration of euglycemia following acute glucose deficit (glucoprivation). Our previous work established that glucoprivic feeding requires ventrolateral medullary (VLM) catecholamine (CA) neurons that coexpress neuropeptide Y (NPY). However, the connections by which VLM CA/NPY neurons trigger increased feeding are uncertain. We have previously shown that glucoprivation, induced by an anti-glycolygic agent 2-deoxy-D-glucose (2DG), activates perifornical lateral hypothalamus (PeFLH) neurons and that expression of NPY in the VLM CA/NPY neurons is required for glucoprivic feeding. We therefore hypothesized that glucoprivic feeding and possibly other CRRs require NPY-sensitive PeFLH neurons. To test this, we used the ribosomal toxin conjugate NPY-saporin (NPY-SAP) to selectively lesion NPY receptor-expressing neurons in the PeFLH of male rats. We found that NPY-SAP destroyed a significant number of PeFLH neurons, including those expressing orexin, but not those expressing melanin-concentrating hormone. The PeFLH NPY-SAP lesions attenuated 2DG-induced feeding but did not affect 2DG-induced increase in locomotor activity, sympathoadrenal hyperglycemia, or corticosterone release. The 2DG-induced feeding response was also significantly attenuated in NPY-SAP-treated female rats. Interestingly, PeFLH NPY-SAP lesioned male rats had reduced body weights and decreased dark cycle feeding, but this effect was not seen in female rats. We conclude that a NPY projection to the PeFLH is necessary for glucoprivic feeding, but not locomotor activity, hyperglycemia, or corticosterone release, in both male and female rats.
摘要：
葡萄糖饲喂是促进急性葡萄糖缺乏后正常血糖恢复的几种反调节反应（CRR）之一（葡萄糖代谢）。我们先前的工作确定，葡萄糖饲喂需要同时表达神经肽Y（NPY）的延髓腹外侧（VLM）儿茶酚胺（CA）神经元。然而,VLMCA/NPY神经元触发增加摄食的连接是不确定的。我们之前已经证明了葡萄糖化，由抗糖能药2-脱氧-D-葡萄糖（2DG）诱导，激活孔周下丘脑外侧（PeFLH）神经元，并且VLMCA/NPY神经元中NPY的表达是葡萄糖饲喂所必需的。因此，我们假设葡萄糖饲喂和其他CRR可能需要NPY敏感的PeFLH神经元。为了测试这个，我们使用了核糖体毒素缀合物,NPY-皂草素（NPY-SAP），选择性损伤雄性大鼠PeFLH中表达NPY受体的神经元。我们发现NPY-SAP破坏了大量的PeFLH神经元,包括那些表达食欲素的，但不是那些表达黑色素浓缩激素的人。PeFLHNPY-SAP病变减弱了2DG诱导的摄食，但不影响2DG诱导的运动活动增加，交感神经肾上腺高血糖症，或皮质酮释放。在NPY-SAP处理的雌性大鼠中,2DG诱导的摄食反应也显著减弱。有趣的是,PeFLHNPY-SAP病变雄性大鼠体重下降，暗周期摄食减少，但是这种效果在雌性大鼠中没有发现。我们得出的结论是，对PeFLH的NPY投影对于葡萄糖饲喂是必要的，但不是运动活动，高血糖症,或皮质酮释放，在雄性和雌性大鼠中。
