Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.
Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.
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DOI：
10.1016/j.molmet.2014.01.014
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发表时间：
2014-07
影响因子：
8.1
通讯作者：
Niswender KD
中科院分区：
文献类型：
--
作者：
Kocalis HE;Hagan SL;George L;Turney MK;Siuta MA;Laryea GN;Morris LC;Muglia LJ;Printz RL;Stanwood GD;Niswender KD
中枢神经系统（CNS）中的胰岛素信号调节能量平衡和外周葡萄糖稳态。Rictor是mTORC 2复合物的关键调节/结构亚基，并且是Akt在丝氨酸473处的疏水基序位点磷酸化所需的。为了检查神经元Rictor/mTORC 2信号传导对CNS调节能量和葡萄糖稳态的贡献，我们利用Cre-LoxP技术产生在所有神经元中或在POMC或AgRP表达神经元中缺乏Rictor的小鼠。所有神经元中Rictor的缺失导致脂肪量增加和肥胖、葡萄糖耐受不良和行为瘦素抵抗。破坏POMC神经元中的Rictor也引起肥胖和暴食、空腹高血糖和明显的葡萄糖耐受不良。AgRP神经元特异性缺失不影响能量平衡，但导致轻度葡萄糖耐受不良。总的来说，我们表明，Rictor/mTORC 2信号，特别是在POMC表达神经元，是重要的中央调节能量和葡萄糖稳态。
Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.
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