Involvement of the Acyl-CoA binding domain containing 7 in the control of food intake and energy expenditure in mice
Involvement of the Acyl-CoA binding domain containing 7 in the control of food intake and energy expenditure in mice
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DOI：
10.7554/elife.11742
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发表时间：
2016-02-15
期刊：
影响因子：
7.7
通讯作者：
Richard, Denis
中科院分区：
文献类型：
--
作者：
Lanfray, Damien;Caron, Alexandre;Richard, Denis
含酰基辅酶A结合结构域7（Acbd 7）是地西泮结合抑制剂/酰基辅酶A结合蛋白的一个同源基因，其中单核苷酸多态性最近被认为与人类肥胖相关。在这份报告中，我们提供了收敛的证据表明，Acbd 7 mRNA的剪接变体亚型的表达和翻译的一些POMC和GABA能神经元在下丘脑弓状核（ARC）。我们已经证明，ARC ACBD 7同种型的产生和加工成一种生物活性肽称为十九碳神经肽（NDN）的分解代谢信号的反应。我们已经将NDN表征为通过未表征的内氮平G蛋白偶联受体并随后通过黑皮质素系统起作用的有效促肾上腺皮质激素信号。我们的研究结果表明，ACBD 7产生神经元参与下丘脑瘦素信号通路。综上所述，这些数据表明，ACBD 7产生神经元参与下丘脑控制施加在食物摄入和能量消耗的瘦素-黑皮质素途径。
Acyl-CoA binding domain-containing 7 (Acbd7) is a paralog gene of the diazepam binding inhibitor/Acyl-CoA binding protein in which single nucleotide polymorphism has recently been associated with obesity in humans. In this report, we provide converging evidence indicating that a splice variant isoform of the Acbd7 mRNA is expressed and translated by some POMC and GABAergic-neurons in the hypothalamic arcuate nucleus (ARC). We have demonstrated that the ARC ACBD7 isoform was produced and processed into a bioactive peptide referred to as nonadecaneuropeptide (NDN) in response to catabolic signals. We have characterized NDN as a potent anorexigenic signal acting through an uncharacterized endozepine G protein-coupled receptor and subsequently via the melanocortin system. Our results suggest that ACBD7producing neurons participate in the hypothalamic leptin signalling pathway. Taken together, these data suggest that ACBD7-producing neurons are involved in the hypothalamic control exerted on food intake and energy expenditure by the leptin-melanocortin pathway.