Sex-divergent effects of hindbrain GLP-1-producing neuron activation in rats.
Sex-divergent effects of hindbrain GLP-1-producing neuron activation in rats.
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DOI：
10.3389/fnins.2023.1265080
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发表时间：
2023
影响因子：
4.3
通讯作者：
Skibicka, Karolina Patrycja
中科院分区：
文献类型：
--
作者：
Lopez-Ferreras, Lorena;Asker, Mohammed;Krieger, Jean-Philippe;Skibicka, Karolina Patrycja
胰高血糖素样肽-1（GLP-1）类似物代表了一类新的减肥药物，最近呈指数增长的流行。GLP-1在肠L细胞中响应于大量营养素摄入而产生，但它也在脑中在孤束核（NTS）中的神经元亚群中产生。外源性GLP-1类似物可减少雄性和雌性大鼠的摄食量和食物动机行为，这些作用在特定脑部位存在一定的性别差异。这些类似物可能靶向由肠道和脑产生的GLP-1内源性提供的GLP-1受体。NTS GLP-1产生神经元[Gcg神经元]的功能在大鼠中仍然相对未知。此外，对这些神经元在女性中的功能了解得更少。我们最近开发了一种转基因大鼠，表达Cre下的Gcg启动子。在这里，我们用光遗传学和化学遗传学询问这种新的动物模型，以确定NTS GLP-1神经元的激活是否会影响雄性和雌性大鼠的摄食和动机行为。NTS Gcg神经元的光遗传激活强烈降低雄性和雌性大鼠的食物摄入量。有趣的是，动机行为的蔗糖奖励减少专门在女性。为了确保这种意外的性别差异不是激活方法特异性的，我们接下来将兴奋性DREADD受体病毒引入Gcg神经元，并研究这些神经元的化学发生激活对摄食和动机行为的影响。即使在化学发生激活后，雌性大鼠降低了获得蔗糖奖励的动机，但在雄性大鼠中没有观察到对这种行为的影响。我们的研究结果表明，激活后脑Gcg神经元是足以减少食物摄入量在两种性别。在女性，但不是男性，Gcg神经元激活单独也足以减少动机行为的蔗糖。因此，GLP-1产生神经元激活控制食物动机行为的能力存在性别差异。
Glucagon-like peptide-1 (GLP-1) analogs represent a new class of weight-loss medication, which has recently exponentially grown in popularity. GLP-1 is produced in the intestinal L cells in response to macronutrient intake, but it is also produced in the brain in a subset of neurons in the nucleus of the solitary tract (NTS). Exogenously-delivered GLP-1 analogs reduce food intake and food-motivated behavior in male and female rats, with some sex divergence of these effects in specific brain sites. These analogs potentially target GLP-1 receptors endogenously supplied by the gut and brain-produced GLP-1. The function of the NTS GLP-1-producing neurons [Gcg neurons] is still relatively unknown in rats. Moreover, even less is understood about the function of these neurons in females. We have recently developed a transgenic rat that expresses Cre under the Gcg promoter. Here, we interrogate this new animal model with optogenetics and chemogenetics to determine whether activation of the NTS GLP-1 neurons affects ingestive and motivated behavior in male and female rats. Optogenetic activation of the NTS Gcg neurons robustly reduced chow intake in both male and female rats. Interestingly, motivated behavior for a sucrose reward was reduced exclusively in females. To ensure that this unexpected sex difference was not activation method-specific, we next virally introduced excitatory DREADD receptors into the Gcg neurons and investigated the effect of chemogenetic activation of these neurons on ingestive and motivated behavior. Even upon chemogenetic activation, female rats reduced their motivation to obtain the sucrose reward, yet no effect on this behavior was observed in males. Our results show that activation of hindbrain Gcg neurons is sufficient to reduce food intake in both sexes. In females, but not males, Gcg neuron activation alone is also sufficient to reduce motivated behavior for sucrose. Thus, there is a sex difference in the ability of GLP-1-producing neuron activation to control motivated behavior for food.
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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.
长效胰高血糖素样肽-1受体激动剂具有直接进入和对小鼠下丘脑中促蛋白酶素/可卡因和苯丙胺刺激的转录物神经元的影响和影响。
影响因子：
3.2
作者：
Knudsen LB;Secher A;Hecksher-Sørensen J;Pyke C
通讯作者：
Pyke C
影响因子：
7.9
作者：
Richard JE;Anderberg RH;López-Ferreras L;Olandersson K;Skibicka KP
通讯作者：
Skibicka KP
DOI：
10.1152/ajpendo.00413.2013
发表时间：
2013-12-01
影响因子：
5.1
作者：
Mietlicki-Baase, Elizabeth G.;Ortinski, Pavel I.;Hayes, Matthew R.
通讯作者：
Hayes, Matthew R.
影响因子：
4.8
作者：
Hayes, Matthew R.;Skibicka, Karolina P.;Grill, Harvey J.
通讯作者：
Grill, Harvey J.