Glutamate release mediates leptin action on energy expenditure.
Glutamate release mediates leptin action on energy expenditure.
复制标题
谷氨酸释放介导瘦素对能量消耗的作用。
DOI：
10.1016/j.molmet.2013.01.004
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发表时间：
2013
影响因子：
8.1
通讯作者：
Tong,Qingchun
中科院分区：
文献类型：
--
作者：
Xu,Yuanzhong;Kim,EunRan;Zhao,Rongjie;MyersJr,MartinG;Munzberg,Heike;Tong,Qingchun
限制能量消耗是对食物短缺的一种适应性反应。尽管瘦素缺乏的小鼠被大量的脂肪组织隔离，但它们失去了维持体温的能力，并发展为深低温，这可以被外源性瘦素抑制，这表明瘦素在能量消耗调节中起重要作用。然而，瘦素作用的机制尚不清楚。我们通过删除这些神经元中的囊泡谷氨酸转运蛋白2来产生从瘦素受体表达神经元中谷氨酸释放中断的小鼠，并发现这些小鼠纯粹由于能量消耗减少而发展为轻度肥胖，表现出快速降低的能量消耗，体温和运动的发作。此外，这些小鼠表现出较低的能量消耗和体温响应于禁食，并在瘦素介导的产热作用在棕色脂肪组织的缺陷。两者合计，我们的研究结果确定了谷氨酸释放在介导瘦素对能量消耗的作用。
Restricting energy expenditure is an adaptive response to food shortage. Despite being insulated with massive amount of fat tissues, leptin-deficient mice lose the ability to maintain their body temperature and develop deep hypothermia, which can be suppressed by exogenous leptin, suggesting an important role for leptin in energy expenditure regulation. However, the mechanism underlying the leptin action is not clear. We generated mice with disruption of glutamate release from leptin receptor-expressing neurons by deleting vesicular glutamate transporter 2 in these neurons, and found that these mice developed mild obesity purely due to reduced energy expenditure, exhibited bouts of rapidly reduced energy expenditure, body temperature and locomotion. In addition, these mice exhibited lower energy expenditure and body temperature in response to fasting and were defective in leptin-mediated thermogenic action in brown adipose tissues. Taken together, our results identify a role for glutamate release in mediating leptin action on energy expenditure.