The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1.
The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1.
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DOI：
10.1126/sciadv.adh0980
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发表时间：
2023-09-22
期刊：
影响因子：
13.6
通讯作者：
Hayes, Matthew R.
中科院分区：
文献类型：
--
作者：
Fortin, Samantha M.;Chen, Jack C.;Petticord, Marisa C.;Ragozzino, Forrest J.;Peters, James H.;Hayes, Matthew R.
增加美国食品药品监督管理局批准的用于治疗肥胖症的胰高血糖素样肽-1受体（GLP-1 R）激动剂的治疗潜力并减少其副作用，需要对介导GLP-1 R信号传导的食物摄入抑制和疾病样作用的中枢机制进行完整表征。我们在大鼠中的研究表明，蓝斑（LC）中的GLP-1 R与摄食量控制相关且具有生理学相关性。此外，LC GLP-1 R的激动作用诱导疾病样行为，LC GLP-1 R的拮抗作用可减弱GLP-1 R介导的恶心。电生理学和行为药理学数据支持突触前神经元能末端表达的LC GLP-1 R在控制进食和不适中的作用。总的来说，我们的工作确立了LC作为GLP-1信号传导的作用位点，并扩展了我们对开发改善肥胖药物疗法所必需的GLP-1信号传导机制的理解。蓝斑参与胰高血糖素样肽-1（GLP-1）信号传导的治疗和副作用。
Increasing the therapeutic potential and reducing the side effects of U.S. Food and Drug Administration–approved glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat obesity require complete characterization of the central mechanisms that mediate both the food intake-suppressive and illness-like effects of GLP-1R signaling. Our studies, in the rat, demonstrate that GLP-1Rs in the locus coeruleus (LC) are pharmacologically and physiologically relevant for food intake control. Furthermore, agonism of LC GLP-1Rs induces illness-like behaviors, and antagonism of LC GLP-1Rs can attenuate GLP-1R–mediated nausea. Electrophysiological and behavioral pharmacology data support a role for LC GLP-1Rs expressed on presynaptic glutamatergic terminals in the control of feeding and malaise. Collectively, our work establishes the LC as a site of action for GLP-1 signaling and extends our understanding of the GLP-1 signaling mechanism necessary for the development of improved obesity pharmacotherapies. The locus coeruleus contributes to the therapeutic and side effects of glucagon-like peptide-1 (GLP-1) signaling.
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DOI：
10.1136/bmj.g2646
发表时间：
2014-05-14
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Dombrowski SU;Knittle K;Avenell A;Araújo-Soares V;Sniehotta FF
通讯作者：
Sniehotta FF
DOI：
10.1523/jneurosci.3262-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dossat AM;Lilly N;Kay K;Williams DL
通讯作者：
Williams DL
影响因子：
2.9
作者：
ELAM, M;THOREN, P;SVENSSON, TH
通讯作者：
SVENSSON, TH
影响因子：
5.3
作者：
Feng, Cheng-Yuan;Wiggins, Larisa M.;von Bartheld, Christopher S.
通讯作者：
von Bartheld, Christopher S.
影响因子：
4.7
作者：
Leon RM;Borner T;Stein LM;Urrutia NA;De Jonghe BC;Schmidt HD;Hayes MR
通讯作者：
Hayes MR