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首页> 外文期刊>American Journal of Physiology >Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism
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Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

机译：下丘脑垂体腺苷酸环化酶激活多肽通过对采食和代谢的位点特异性作用调节能量平衡

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Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei, suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites; however, meal pattern analysis revealed that only injections into the PVN produced significant reductions in meal size, duration, and total time spent eating. PACAP-mediated hypophagia in both the PVN and VMN was abolished by PAC1R antagonism, whereas pretreatment with a VPACR antagonist had no effect. PACAP injections into the VMN produced unique changes in metabolic parameters, including significant increases in core body temperature and spontaneous locomotor activity that was PAC1R dependent whereas, PVN injections of PACAP had no effect. Finally, PACAP-containing afferents were identified using the neuronal tracer cholera toxin subunit B (CTB) injected unilaterally into the PVN or VMN. CTB signal from PVN injections was colocalized with PACAP mRNA in the medial anterior bed nucleus of the stria terminalis, VMN, and lateral parabrachial nucleus (LPB), whereas CTB signal from VMN injections was highly colocalized with PACAP mRNA in the medial amygdala and LPB. These brain regions are known to influence energy homeostasis perhaps, in part, through PACAP projections to the PVN and VMN.
机译：大量研究表明，下丘脑室旁核（PVN）和腹膜外核（VMN）均通过行为和代谢机制调节能量稳态。垂体腺苷酸环化酶激活多肽（PACAP）的受体在这些细胞核中大量表达，表明PACAP对于调节喂养行为和体重可能至关重要。为了表征归因于选择的下丘脑细胞群的独特行为和生理反应，将PACAP位点特异性注入PVN或VMN中。两个地点的PACAP显着降低了总体食物摄入量;但是，进餐模式分析显示，只有向PVN注射才能显着减少进餐量，进餐时间和总进餐时间。 PAC1R拮抗作用消除了PVN和VMN中PACAP介导的吞咽不足，而用VPACR拮抗剂进行预处理则无效。 PACAP注射到VMN中会产生代谢参数的独特变化，包括核心体温的显着升高和PAC1R依赖的自发运动能力，而PVN注射的PACAP没有作用。最后，使用单侧注射到PVN或VMN中的神经元示踪霍乱毒素亚基B（CTB）鉴定了含有PACAP的传入物质。来自PVN注射的CTB信号与PACAP mRNA共同位于终末纹，VMN和臂外侧臂旁核（LPB）的内侧前核中，而来自VMN注射的CTB信号与PACAP mRNA高度位于杏仁体和LPB的内侧。已知这些大脑区域可能部分地通过PACAP对PVN和VMN的预测来影响能量稳态。

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