Liraglutide Modulates Appetite and Body Weight Through Glucagon-Like Peptide 1 Receptor-Expressing Glutamatergic Neurons.
Liraglutide Modulates Appetite and Body Weight Through Glucagon-Like Peptide 1 Receptor-Expressing Glutamatergic Neurons.
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作者：
Adams JM;Pei H;Sandoval DA;Seeley RJ;Chang RB;Liberles SD;Olson DP
胰高血糖素样肽1受体（GLP-1 R）激动剂是美国食品和药物管理局批准的减肥药物。尽管GLP-1 R激动剂（GLP 1 RA）被广泛使用，但其影响食欲和体重的作用部位仍不完全清楚。我们确定了GABA能或谷氨酸能神经元中的GLP-1 R是否是GLP 1 RA利拉鲁肽对摄食量、内脏疾病、体重和神经网络激活的短期和长期影响所必需的。我们发现，在表达vGAT的GABA能神经元中缺乏GLP-1 Rs的小鼠在所有测量参数中的反应与对照组相同，而在表达vGlut 2的GABA能神经元中缺失GLP-1 Rs消除了利拉鲁肽诱导的体重减轻和内脏疾病，并严重减弱了其对进食的影响。同时，从多巴胺能神经元中删除GLP-1 R完全消除了利拉鲁肽给药后观察到的神经网络激活。我们得出结论，利拉鲁肽激活分散但离散的神经网络以介导其生理效应，并且这些效应需要GLP-1 R在谷氨酸能神经元而非GABA能神经元上表达。
Glucagon-like peptide 1 receptor (GLP-1R) agonists are U.S. Food and Drug Administration–approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) affect appetite and body weight are still not fully understood. We determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the short- and long-term effects of the GLP1RA liraglutide on food intake, visceral illness, body weight, and neural network activation. We found that mice lacking GLP-1Rs in vGAT-expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in vGlut2-expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding. Concomitantly, deletion of GLP-1Rs from glutamatergic neurons completely abolished the neural network activation observed after liraglutide administration. We conclude that liraglutide activates a dispersed but discrete neural network to mediate its physiological effects and that these effects require GLP-1R expression on glutamatergic but not GABAergic neurons.
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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：
3.3
作者：
Llewellyn-Smith, I. J.;Reimann, F.;Gribble, F. M.;Trapp, S.
通讯作者：
Trapp, S.
下丘脑胰高血糖素样肽1受体足够，但对于调节小鼠的能量平衡和葡萄糖稳态不需要。
影响因子：
7.7
作者：
Burmeister MA;Ayala JE;Smouse H;Landivar-Rocha A;Brown JD;Drucker DJ;Stoffers DA;Sandoval DA;Seeley RJ;Ayala JE
通讯作者：
Ayala JE
DOI：
10.1152/ajpregu.00424.2010
发表时间：
2011-10-01
影响因子：
2.8
作者：
Baraboi, Elena-Dana;St-Pierre, David H.;Richard, Denis
通讯作者：
Richard, Denis
影响因子：
7.7
作者：
Krieger, Jean-Philippe;Arnold, Myrtha;Lee, Shin J.
通讯作者：
Lee, Shin J.