来自美国哈佛医学院的Bradford B. Lowell实验室发现弧形的核中GABAergic RIP-Cre神经元选择性的调节能量消耗,本篇文章刊登在最新一期《CELL》杂志上。

-2012年10月26日《细胞》


中文翻译


【题目】在弧形的核中GABAergic RIP-Cre神经元选择性的调节能量消耗

【译文】能量消耗的神经调节还没能被科学家们研究清楚。我们通过在细胞专一性的模型中破坏GABAergic的传输并把这与选择性的遗传药理学活性和光遗传图谱技术结合,发现了一种选择性驱动能量消耗的基于弧形的回路。特别的是,缺乏从RIP-Cre神经元释放的联合的GABA小鼠可以减少能量消耗,这种小鼠易患肥胖症并且对高脂肪饮食引起的肥胖症极端敏感,后者是由于缺乏膳食引起的产热而形成的肥胖症。来普汀可以刺激产热,但是不能减少食物摄取,而这就减弱了其作用。弧形的GABAergic RIP-Cre神经元(单突触的刺激映射到NTS上的PVH神经元)的选择性激活可以快速刺激褐色脂肪组织并且增加能量消耗,但不能影响食物摄取。重要的是这一反应依赖于从RIP-Cre神经元释放的GABA。因此,GABAergic RIP-Cre神经元选择性驱动能量消耗过程中对于来普汀刺激产生的生热作用发挥作用并且可以防止由饮食诱导的肥胖症的发生。

英文原稿


[Title]GABAergic RIP-Cre Neurons in the Arcuate Nucleus Selectively Regulate Energy Expenditure

[Authors]Dong Kong, Qingchun Tong, Chianping Ye, Shuichi Koda, Patrick M. Fuller, Michael J. Krashes, Linh Vong, Russell S. Ray, David P. Olson, Bradford B. Lowell

[Abstract]Neural regulation of energy expenditure is incompletely understood. By genetically disrupting GABAergic transmission in a cell-specific fashion, and by combining this with selective pharmacogenetic activation and optogenetic mapping techniques, we have uncovered an arcuate-based circuit that selectively drives energy expenditure. Specifically, mice lacking synaptic GABA release from RIP-Cre neurons have reduced energy expenditure, become obese and are extremely sensitive to high-fat diet-induced obesity, the latter due to defective diet-induced thermogenesis. Leptin’s ability to stimulate thermogenesis, but not to reduce feeding, is markedly attenuated. Acute, selective activation of arcuate GABAergic RIP-Cre neurons, which monosynaptically innervate PVH neurons projecting to the NTS, rapidly stimulates brown fat and increases energy expenditure but does not affect feeding. Importantly, this response is dependent upon GABA release from RIP-Cre neurons. Thus, GABAergic RIP-Cre neurons in the arcuate selectively drive energy expenditure, contribute to leptin’s stimulatory effect on thermogenesis, and protect against diet-induced obesity.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01127-0

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