2012年10月2日 訊 /生物谷BIOON/ --對很多人來說,，保持健康的體重可能是困難的,，現(xiàn)在有研究證實我們的大腦和機(jī)體能一起工作調(diào)控體重，可以實現(xiàn)一個能源平衡現(xiàn)象,。這種平衡可能是由于大腦下丘腦區(qū)域神經(jīng)生物學(xué)功能交互作用的結(jié)果,，而這個交互作用一旦出現(xiàn)差錯時，就會出現(xiàn)肥胖或厭食現(xiàn)象,。
很少有人知道這個復(fù)雜的交互作用細(xì)節(jié)?，F(xiàn)在，以色列女執(zhí)事醫(yī)療中心（BIDMC）研究人員開展的一項新研究為這種復(fù)雜性提供了新的見解,。相關(guān)研究結(jié)果發(fā)表在10月26日的Cell雜志上,，研究結(jié)果主要揭示了GABA神經(jīng)遞質(zhì)是如何有選擇地調(diào)控能源平衡，明白其中機(jī)制有助于解釋棕色脂肪的燃燒性能,。
研究人員已經(jīng)建成了大腦中一個控制食欲和燃燒熱量的神經(jīng)線路圖,，為了實現(xiàn)這一目的，我們需要知道特定亞群的神經(jīng)元功能,，上游神經(jīng)元的輸入信號和下游神經(jīng)元的輸出信號,。下丘腦是大腦中能量平衡控制中心，這種平衡的結(jié)果是由大腦接收反饋信號,，然后整合外部信號的輸入共同完成的,。
在這項新研究中，研究人員調(diào)查了大腦中下丘腦弓狀核神經(jīng)元。利用基因缺陷工程小鼠（神經(jīng)元釋放抑制性神經(jīng)遞質(zhì)GABA）,，這一缺陷的小鼠會顯著出現(xiàn)肥胖現(xiàn)象,，值得注意的是，他們的肥胖完全是因為燃燒熱量功能缺陷而導(dǎo)致的,，這些小鼠的食物的攝入量是完全不受影響的。
研究人員發(fā)現(xiàn)當(dāng)他們開啟大腦中神經(jīng)元時,，能量的消耗完全取決于GABA的釋放,。這些結(jié)果揭示了，弓狀核神經(jīng)元調(diào)控GABA的釋放,，影響能源開支?，F(xiàn)在重要的是要充分劃定控制產(chǎn)熱的弓形神經(jīng)元，構(gòu)建出一個清晰明確的調(diào)控網(wǎng)絡(luò)圖,，開發(fā)有效的肥胖及其相關(guān)并發(fā)癥的治療方法,。（生物谷：Bioon.com）
doi:10.1016/j.cell.2012.09.020
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GABAergic RIP-Cre Neurons in the Arcuate Nucleus Selectively Regulate Energy Expenditure
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
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. Leptins 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 leptins stimulatory effect on thermogenesis, and protect against diet-induced obesity.
