Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake.
Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake.
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作者：
Gardiner JV;Bataveljic A;Patel NA;Bewick GA;Roy D;Campbell D;Greenwood HC;Murphy KG;Hameed S;Jethwa PH;Ebling FJ;Vickers SP;Cheetham S;Ghatei MA;Bloom SR;Dhillo WS
前动力蛋白2（PK 2）是一种下丘脑神经肽，在已知参与食物摄入的中枢神经系统区域中表达。因此，我们假设PK 2在能量稳态中起作用。我们通过侧脑室注射PK 2和抗PK 2抗体，研究了营养状况对下丘脑PK 2表达的影响以及PK 2对摄食调节的影响。随后，我们通过确定ICV注射PK 2后神经元激活的位点、PK 2的下丘脑作用位点以及PK 2与调节能量稳态的其他下丘脑神经肽之间的相互作用来研究潜在的作用机制。为了研究PK 2作为治疗靶点的潜力，我们研究了长期给药对瘦小鼠和肥胖小鼠的影响。禁食可降低下丘脑PK 2表达。ICV给予大鼠PK 2有效地抑制食物摄入，而抗PK 2抗体增加食物摄入，表明PK 2是一种厌食神经肽。ICV给药PK 2增加了下丘脑弓状核（ARC）前阿黑皮素神经元中c-fos的表达。与此一致，ARC中给予PK 2减少了食物摄入，PK 2增加了离体下丘脑外植体中α-促黑素细胞激素（α-MSH）的释放。此外，ICV与α-MSH拮抗剂刺豚鼠相关肽联合给药可阻断PK 2的促凋亡作用。PK 2的慢性外周给药减少了瘦小鼠和肥胖小鼠的食物和体重。这是第一个报告表明，PK 2在食欲调节中发挥作用，其厌食作用部分是通过黑皮质素系统介导的。
Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2's potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice. Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of α-melanocyte–stimulating hormone (α-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the α-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice. This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system.
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影响因子：
64.8
作者：
Cheng, MY;Bullock, CM;Zhou, QY
通讯作者：
Zhou, QY
影响因子：
--
作者：
McGowan, B. M.;Stanley, S. A.;Bloom, S. R.
通讯作者：
Bloom, S. R.
影响因子：
4.8
作者：
Dhillo, WS;Small, CJ;Bloom, SR
通讯作者：
Bloom, SR
DOI：
10.1152/ajpendo.00332.2001
发表时间：
2002-04-01
影响因子：
5.1
作者：
Burcelin, M;Crivelli, V;Thorens, B
通讯作者：
Thorens, B
影响因子：
7.7
作者：
Kim, MS;Rossi, M;Bloom, SR
通讯作者：
Bloom, SR