A role of phosphodiesterase-3B pathway in mediating leptin action on proopiomelanocortin and neurotensin neurons in the hypothalamus.
A role of phosphodiesterase-3B pathway in mediating leptin action on proopiomelanocortin and neurotensin neurons in the hypothalamus.
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磷酸二酯酶-3B 通路在介导瘦素对下丘脑阿黑皮素原和神经降压素神经元的作用中的作用。
DOI：
10.1016/j.neulet.2010.05.018
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发表时间：
2010-07-19
影响因子：
2.5
通讯作者：
Sahu, Abhiram
中科院分区：
文献类型：
--
作者：
Sahu, Abhiram
下丘脑中的瘦素信号传导是正常食物摄入和体重稳态所必需的。最近的证据表明，除了信号转导子和转录激活子3（STAT 3）途径，一些非STAT 3途径介导的瘦素信号在下丘脑。我们以前已经证明，瘦素刺激磷酸二酯酶-3B（PDE 3B）在下丘脑的活性，和PDE 3抑制剂西洛酰胺逆转瘦素的厌食和体重减轻的影响。为了确定PDE 3B信号在下丘脑中的生理作用，我们检查了通过PDE 3B途径的瘦素信号是否负责阿黑皮素原（POMC）和神经降压素（NT）神经元的激活，这两种神经元已知在能量稳态中起关键作用。为此，我们评估了西洛酰胺对瘦素诱导的大鼠下丘脑POMC和NT基因表达的影响。结果表明，虽然中央注射瘦素显着增加POMC和NT的mRNA水平在内侧基底下丘脑，西洛酰胺完全逆转这种效果的瘦素表明PDE 3B激活依赖诱导POMC和NT基因表达的瘦素。这一结果进一步表明，PDE 3B通路在介导下丘脑中的瘦素作用中起重要作用。
Leptin signaling in the hypothalamus is required for normal food intake and body weight homeostasis. Recent evidence suggests that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways mediate leptin signaling in the hypothalamus. We have previously demonstrated that leptin stimulates phosphodiesterase-3B (PDE3B) activity in the hypothalamus, and PDE3 inhibitor cilostamide reverses anorectic and bodyweight reducing effects of leptin. To establish the physiological role of PDE3B signaling in the hypothalamus, we examined if leptin signaling through the PDE3B pathway is responsible for the activation of proopiomelanocortin (POMC) and neurotensin (NT) neurons, which are known to play a critical role in energy homeostasis. To this end, we assessed the effect of cilostamide on leptin-induced POMC and NT gene expression in the rat hypothalamus. Results showed that while central injection of leptin significantly increased both POMC and NT mRNA levels in the medial basal hypothalamus, cilostamide completely reversed this effect of leptin suggesting a PDE3B-activation dependent induction of POMC and NT gene expression by leptin. This result further suggests that the PDE3B pathway plays an important role in mediating leptin action in the hypothalamus.
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影响因子：
29
作者：
Al-Qassab H;Smith MA;Irvine EE;Guillermet-Guibert J;Claret M;Choudhury AI;Selman C;Piipari K;Clements M;Lingard S;Chandarana K;Bell JD;Barsh GS;Smith AJ;Batterham RL;Ashford ML;Vanhaesebroeck B;Withers DJ
通讯作者：
Withers DJ
影响因子：
56.9
作者：
Cota, D;Proulx, K;Seeley, RJ
通讯作者：
Seeley, RJ
DOI：
10.1073/pnas.93.13.6231
发表时间：
1996-06-25
影响因子：
11.1
作者：
Ghilardi, N;Ziegler, S;Skoda, RC
通讯作者：
Skoda, RC
影响因子：
16.2
作者：
Elias, CF;Aschkenasi, C;Elmquist, JK
通讯作者：
Elmquist, JK
影响因子：
5.3
作者：
Hübschle, T;Thom, E;Meyerhof, W
通讯作者：
Meyerhof, W