Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus.
Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus.
复制标题
DOI：
10.1016/j.ygcen.2018.10.008
复制
发表时间：
2019-01-01
影响因子：
2.7
通讯作者：
Currie PJ
中科院分区：
文献类型：
--
作者：
Abtahi S;Howell E;Salvucci JT;Bastacky JMR;Dunn DP;Currie PJ
在本研究中，我们研究了下丘脑室旁核（PVN）胰高血糖素样肽-1 （GLP-1）和胃饥饿素信号在代谢功能控制中的相互作用。我们首先证明，直接注射到PVN的酰化胃饥饿素可靠地改变了成年雄性斯普拉格道利大鼠的呼吸交换率（RER）。所有测试均在夜间周期的最初2小时使用间接开路量热计进行。结果表明，酰化胃饥饿素诱导内质网显著增加，代表了碳水化合物氧化增强和脂质利用减少的转变。相比之下，同等剂量的去酰基胃饥饿素治疗未能显著影响代谢活性。在不同的大鼠组中，我们随后研究了exendin-4 （GLP-1类似物）改变酰化胃饥饿素代谢作用的能力。小鼠分别全身或直接注射PVN Ex-4，然后注射酰基胃饥饿素显微注射。虽然我们的研究结果表明，全身和PVN给药Ex-4都能显著降低内质网，但重要的是，Ex-4预处理本身可靠地抑制了胃饥饿素对内质网的影响。总的来说，这些发现提供了越来越令人信服的证据，证明GLP-1和胃饥饿素信号在PVN内代谢功能的神经控制中相互作用。
In the current study we investigated the interaction of hypothalamic paraventricular nucleus (PVN) glucagon-like peptide-1 (GLP-1) and ghrelin signaling in the control of metabolic function. We first demonstrated that acylated ghrelin injected directly into the PVN reliably altered the respiratory exchange ratio (RER) of adult male Sprague Dawley rats. All testing was carried out during the initial 2 h of the nocturnal cycle using an indirect open circuit calorimeter. Results indicated that acylated ghrelin induced a robust increase in RER representing a shift toward enhanced carbohydrate oxidation and reduced lipid utilization. In contrast, treatment with comparable dosing of des-acyl ghrelin failed to significantly impact metabolic activity. In separate groups of rats we subsequently investigated the ability of exendin-4 (Ex-4), a GLP-1 analogue, to alter acylated ghrelin’s metabolic effects. Rodents were treated with either systemic or direct PVN Ex-4 followed by acyl ghrelin microinjection. While our results showed that both systemic and PVN administration of Ex-4 significantly reduced RER, importantly, Ex-4 pretreatment itself reliably inhibited the impact of ghrelin on RER. Overall, these findings provide increasingly compelling evidence that GLP-1 and ghrelin signaling interact in the neural control of metabolic function within the PVN.
登录
查看更多内容
影响因子：
3.2
作者：
Delporte C
通讯作者：
Delporte C
影响因子：
4.3
作者：
Delgado MJ;Cerdá-Reverter JM;Soengas JL
通讯作者：
Soengas JL
影响因子：
4.8
作者：
Dalvi, Prasad S.;Nazarians-Armavil, Anaies;Belsham, Denise D.
通讯作者：
Belsham, Denise D.
影响因子：
3.7
作者：
Cabral A;Portiansky E;Sánchez-Jaramillo E;Zigman JM;Perello M
通讯作者：
Perello M
影响因子：
3.2
作者：
Fernandez, G.;Cabral, A.;Perello, M.
通讯作者：
Perello, M.