Hypothalamic POMC neurons promote cannabinoid-induced feeding.
Hypothalamic POMC neurons promote cannabinoid-induced feeding.
复制标题
DOI：
10.1038/nature14260
复制
发表时间：
2015-03-05
期刊：
影响因子：
64.8
通讯作者：
Horvath, Tamas L.
中科院分区：
文献类型：
--
作者：
Koch, Marco;Varela, Luis;Kim, Jae Geun;Kim, Jung Dae;Hernandez-Nuno, Francisco;Simonds, Stephanie E.;Castorena, Carlos M.;Vianna, Claudia R.;Elmquist, Joel K.;Morozov, Yury M.;Rakic, Pasko;Bechmann, Ingo;Cowley, Michael A.;Szigeti-Buck, Klara;Dietrich, Marcelo O.;Gao, Xiao-Bing;Diano, Sabrina;Horvath, Tamas L.
下丘脑促鸦片黑素皮质素（POMC）神经元促进饱腹感。大麻素受体1 （CB1R）对食物摄入的中枢调节至关重要。我们询问cb1r控制的摄食是否与POMC神经元活性下降有关。化学促进CB1R活性增加了摄食，并且CB1R激活也显著促进了POMC细胞的神经元活性。这种POMC活性的增加对cb1r诱导的摄食至关重要，因为设计药物特异性激活的设计受体（DREADD）介导的POMC神经元抑制减弱，而DREADD介导的POMC神经元激活增强了cb1r驱动的摄食。Pomc基因编码厌氧肽α-促黑素细胞激素（α-MSH）和肽β-内啡肽。CB1R的激活选择性地增加了下丘脑中β-内啡肽的释放，而不是α-MSH的释放，并且，全身或下丘脑给予阿片受体拮抗剂纳洛酮，阻断了CB1R诱导的急性喂养。这些过程涉及线粒体适应，当线粒体适应被阻断时，就会消除cb1r诱导的细胞反应和摄食。总之，这些结果揭示了POMC神经元在促进大麻素喂养中的一个以前未被怀疑的作用。
Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for central regulation of food intake. We interrogated whether CB1R-controlled feeding is paralleled by decreased activity of POMC neurons. Chemical promotion of CB1R activity increased feeding, and strikingly, CB1R activation also promoted neuronal activity of POMC cells. This paradoxical increase in POMC activity was crucial for CB1R-induced feeding, because Designer-Receptors-Exclusively-Activated-by-Designer-Drugs (DREADD)-mediated inhibition of POMC neurons diminished, while DREADD-mediated activation of POMC neurons enhanced CB1R-driven feeding. The Pomc gene encodes both the anorexigenic peptide, α-melanocyte-stimulating hormone (α-MSH), and the peptide, β-endorphin. CB1R activation selectively increased β-endorphin but not α-MSH release in the hypothalamus, and, systemic or hypothalamic administration of the opioid receptor antagonist, naloxone, blocked acute CB1R-induced feeding. These processes involved mitochondrial adaptations, which, when blocked, abolished CB1R-induced cellular responses and feeding. Together, these results unmasked a previously unsuspected role of POMC neurons in promotion of feeding by cannabinoids.
登录
查看更多内容
DOI：
10.1523/jneurosci.3890-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Andrews ZB;Erion D;Beiler R;Liu ZW;Abizaid A;Zigman J;Elsworth JD;Savitt JM;DiMarchi R;Tschoep M;Roth RH;Gao XB;Horvath TL
通讯作者：
Horvath TL
影响因子：
25
作者：
Dietrich, Marcelo O.;Bober, Jeremy;Horvath, Tamas L.
通讯作者：
Horvath, Tamas L.
影响因子：
16.2
作者：
Elias, CF;Aschkenasi, C;Elmquist, JK
通讯作者：
Elmquist, JK
影响因子：
4.8
作者：
HORVATH, TL;NAFTOLIN, F;LERANTH, C
通讯作者：
LERANTH, C
影响因子：
64.8
作者：
Fan, W;Boston, BA;Cone, RD
通讯作者：
Cone, RD