Integrative and Translational Physiology : Integrative Aspects of Energy Homeostasis and Metabolic Diseases Stimulation of the hypothalamic ventromedial nuclei by pituitary adenylate cyclase-activating polypeptide induces hypophagia and thermogenesis
Integrative and Translational Physiology : Integrative Aspects of Energy Homeostasis and Metabolic Diseases Stimulation of the hypothalamic ventromedial nuclei by pituitary adenylate cyclase-activating polypeptide induces hypophagia and thermogenesis
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发表时间：
2011
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通讯作者：
J. Resch;J. Boisvert;Allison E Hourigan;Christopher R. Mueller;S. Yi;SuJean Choi
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作者：
J. Resch;J. Boisvert;Allison E Hourigan;Christopher R. Mueller;S. Yi;SuJean Choi
结果JM，Boisvert JP，Hourigan AE，Mueller CR，Yi SS，Choi S。用垂体腺苷环化酶激活多肽刺激下丘脑腹内侧核可引起吞噬功能减退和产热。Am J Physiol Regul Integr Comp Physiol 301：R1625-R1634,2011.2011年9月28日首次出版；DOI：10.1152/ajpregu.00334.2011。-大量研究表明，下丘脑腹内侧核(VMN)通过整合和利用行为和代谢机制来调节能量稳态。VMN大量表达垂体腺苷环化酶激活多肽(PACAP)I型受体(PAC1R)。尽管有受体的分布，但大多数研究摄食影响的PACAP实验都集中在脑室内给药或全局基因敲除小鼠上。为了确定PACAP信号在VMN中的具体作用，我们将PACAP直接注射到VMN中，并测量了取食行为和能量消耗指数。在急性注射PACAP后，在注射后6小时内夜间进食量显著减少，但没有不适迹象。此外，PACAP诱导的摄食抑制也发生在隔夜禁食之后，并可被特定的PAC1R拮抗剂阻断。在代谢方面，VMN特异性注射PACAP显著增加核心体温和自发活动，同时增加棕色脂肪解偶联蛋白1mRNA的表达。为了确定哪些信号通路对PACAP进入VMN有反应，我们测量了具有良好特征的下丘脑摄食神经肽调节器的mRNA表达。注射PACAP 1h后，弓状核(ARC)前阿片黑素皮质素基因表达显著增加，神经肽Y和刺鼠相关多肽基因表达无明显变化。这表明，PAC1R表达的VMN神经元投射到前阿片黑素皮质素神经元，参与了黑素皮质素信号转导，从而导致了吞噬功能低下。虽然VMN也大量表达PACAP蛋白，但本研究表明，向VMN输入PACAP可以影响能量平衡的控制。
Resch JM, Boisvert JP, Hourigan AE, Mueller CR, Yi SS, Choi S. Stimulation of the hypothalamic ventromedial nuclei by pituitary adenylate cyclase-activating polypeptide induces hypophagia and thermogenesis. Am J Physiol Regul Integr Comp Physiol 301: R1625–R1634, 2011. First published September 28, 2011; doi:10.1152/ajpregu.00334.2011.— Numerous studies have demonstrated that the hypothalamic ventromedial nuclei (VMN) regulate energy homeostasis by integrating and utilizing behavioral and metabolic mechanisms. The VMN heavily express pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptors (PAC1R). Despite the receptor distribution, most PACAP experiments investigating affects on feeding have focused on intracerebroventricular administration or global knockout mice. To identify the specific contribution of PACAP signaling in the VMN, we injected PACAP directly into the VMN and measured feeding behavior and indices of energy expenditure. Following an acute injection of PACAP, nocturnal food intake was significantly reduced for 6 h after injections without evidence of malaise. In addition, PACAP-induced suppression of feeding also occurred following an overnight fast and could be blocked by a specific PAC1R antagonist. Metabolically, VMN-specific injections of PACAP significantly increased both core body temperature and spontaneous locomotor activity with a concurrent increase in brown adipose uncoupling protein 1 mRNA expression. To determine which signaling pathways were responsive to PACAP administration into the VMN, we measured mRNA expression of well-characterized hypothalamic neuropeptide regulators of feeding. One hour after PACAP administration, expression of proopiomelanocortin mRNA was significantly increased in the arcuate nuclei (ARC), with no changes in neuropeptide Y and agouti-related polypeptide mRNA levels. This suggests that PAC1R expressing VMN neurons projecting to pro-opiomelanocortin neurons contribute to hypophagia by involving melanocortin signaling. While the VMN also abundantly express PACAP protein, the present study demonstrates that PACAP input to the VMN can influence the control of energy homeostasis.