Acute high fat diet consumption activates the mesolimbic circuit and requires orexin signaling in a mouse model.

Acute high fat diet consumption activates the mesolimbic circuit and requires orexin signaling in a mouse model.
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DOI:
10.1371/journal.pone.0087478
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Perello M
Perello M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Valdivia S;Patrone A;Reynaldo M;Perello M

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过度食用美味的高能量食物对健康有负面影响,它与肥胖和几种饮食失调有关。目前,人们对急性摄取有益刺激所激活的神经元回路知之甚少。在这里,我们使用免疫组织化学、药理学和神经元示踪分析的组合来检查中边缘系统的作用,特别是食欲素神经元,在一个简单的实验测试中,naïve小鼠被允许自发地吃高脂肪饮食(HFD) 2小时。我们发现急性HFD激活了几个与奖励相关的大脑区域的c-Fos表达,包括腹侧被压区(VTA)、伏隔核、中央杏仁核和外侧下丘脑区。我们还发现:1 - HFD介导的口感觉刺激是中边缘通路激活所必需的,2 -急性HFD不同程度地激活了VTA的神经旁区、臂旁色素区和束间亚区多巴胺神经元,iii-下丘脑外侧区域的食欲素神经元对急性HFD有反应。此外,与食欲素1受体拮抗剂SB-334867一起,食欲素信号阻断可以减少VTA的急性HFD消耗和c-Fos诱导,但在研究的其他中边缘核中没有。最后,我们发现大多数对急性HFD有反应的食欲素神经元支配VTA。我们的研究结果表明,急性高脂肪摄入会激活中脑边缘系统,而这种饮食行为的充分表现需要激活食欲素信号。
Overconsumption of palatable energy-dense foods has negative health implications and it is associated with obesity and several eating disorders. Currently, little is known about the neuronal circuitries activated by the acute ingestion of a rewarding stimulus. Here, we used a combination of immunohistochemistry, pharmacology and neuronal tracing analyses to examine the role of the mesolimbic system in general, and the orexin neurons in particular, in a simple experimental test in which naïve mice are allowed to spontaneously eat a pellet of a high fat diet (HFD) for 2 h. We found that acute HFD activates c-Fos expression in several reward-related brain areas, including the ventral tegmental area (VTA), nucleus accumbens, central amygdala and lateral hypothalamic area. We also found that: i- HFD-mediated orosensory stimulation was required for the mesolimbic pathway activation, ii- acute HFD differentially activates dopamine neurons of the paranigral, parabrachial pigmented and interfascicular sub-regions of the VTA, and iii- orexin neurons of the lateral hypothalamic area are responsive to acute HFD. Moreover, orexin signaling blockade, with the orexin 1 receptor antagonist SB-334867, reduces acute HFD consumption and c-Fos induction in the VTA but not in the other mesolimbic nuclei under study. Finally, we found that most orexin neurons responsive to acute HFD innervate the VTA. Our results show that acute HFD consumption recruits the mesolimbic system and that the full manifestation of this eating behavior requires the activation of orexin signaling.
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