Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons.
Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons.
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DOI：
10.1016/j.molmet.2016.08.007
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发表时间：
2016-10
影响因子：
8.1
通讯作者：
Williams KW
中科院分区：
文献类型：
--
作者：
Sun J;Gao Y;Yao T;Huang Y;He Z;Kong X;Yu KJ;Wang RT;Guo H;Yan J;Chang Y;Chen H;Scherer PE;Liu T;Williams KW
脂联素受体（AdipoRs）位于下丘脑参与代谢调节的神经元上，包括弓形原皮质素（Pomc）和神经肽Y/ agouti相关肽（NPY/AgRP）神经元。adipor通过启动与瘦素受体（lepr）重叠的信号级联反应，在调节葡萄糖和脂肪酸代谢中发挥关键作用。然而，脂联素调节大脑细胞活动的机制仍不清楚。为了解决这一问题，我们利用神经元特异性转基因小鼠模型，鉴定表达lepr的Pomc和NPY/AgRP神经元，进行片钳电生理实验。我们发现瘦素和脂联素协同激活弓状核中的黑素皮质素神经元。相反，NPY/AgRP神经元对脂联素的反应受到抑制。脂联素诱导的弓形Pomc神经元的去极化是通过激活磷酸肌苷-3激酶（PI3K）信号而发生的，不依赖于5 ' amp激活的蛋白激酶（AMPK）活性。在不同的生理葡萄糖水平下，脂联素也能激活黑素皮质素神经元。我们的研究结果表明，在急性脂联素诱导的对弓形黑素皮质素神经元细胞活性的影响中，PI3K信号通路是必需的。此外，这些数据为PI3K作为瘦素和脂联素的底物通过黑素皮质素活性调节能量平衡和葡萄糖代谢提供了证据。脂联素激活弓形Pomc神经元。脂联素诱导的Pomc神经元激活需要PI3K（独立于AMPK）。脂联素抑制邻近的NPY/AgRP神经元（去抑制弓形Pomc神经元）。瘦素增强脂联素对Pomc神经元的影响。
Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity. Adiponectin activates arcuate Pomc neurons. Adiponectin-induced activation of Pomc neurons requires PI3K (independent of AMPK). Adiponectin inhibits adjacent NPY/AgRP neurons (disinhibiting arcuate Pomc neurons). Leptin potentiates the effects of adiponectin arcuate Pomc neurons.
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影响因子：
29
作者：
Kajimura D;Lee HW;Riley KJ;Arteaga-Solis E;Ferron M;Zhou B;Clarke CJ;Hannun YA;DePinho RA;Guo XE;Mann JJ;Karsenty G
通讯作者：
Karsenty G
影响因子：
16.2
作者：
Elias, CF;Aschkenasi, C;Elmquist, JK
通讯作者：
Elmquist, JK
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作者：
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通讯作者：
Bruening, Jens C.
影响因子：
2.9
作者：
Alim, Ishraq;Fry, W. Mark;Ferguson, Alastair V.
通讯作者：
Ferguson, Alastair V.
影响因子：
29
作者：
Kubota, Naoto;Yano, Wataru;Kadowaki, Takashi
通讯作者：
Kadowaki, Takashi