AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.
AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.
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DOI：
10.1016/j.cell.2016.02.044
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发表时间：
2016-03-24
期刊：
影响因子：
64.5
通讯作者：
Bruening, Jens C.
中科院分区：
文献类型：
--
作者：
Steculorum, Sophie M.;Ruud, Johan;Karakasilioti, Ismene;Backes, Heiko;Ruud, Linda Engstroem;Timper, Katharina;Hess, Martin E.;Tsaousidou, Eva;Mauer, Jan;Vogt, Merly C.;Paeger, Lars;Bremser, Stephan;Klein, Andreas C.;Morgan, Donald A.;Frommolt, Peter;Brinkkoetter, Paul T.;Hammerschmidt, Philipp;Benzing, Thomas;Rahmouni, Kamal;Wunderlich, F. Thomas;Kloppenburg, Peter;Bruening, Jens C.
刺豚鼠相关肽 (AgRP) 神经元的激活可有效促进进食，长期改变其活性也会影响外周葡萄糖稳态。我们证明 AgRP 神经元的急性激活通过损害胰岛素刺激的棕色脂肪组织 (BAT) 的葡萄糖摄取而导致胰岛素抵抗。 AgRP 神经元激活可急剧地将 BAT 中的基因表达重新编程为肌原性特征，包括肌生长抑制素表达的增加。干扰肌生长抑制素活性可改善因 AgRP 神经元激活而受损的胰岛素敏感性。光遗传学电路图显示，进食和胰岛素敏感性是由不同和重叠的投影控制的。 AgRP → LHA 投射的刺激会损害胰岛素敏感性并促进摄食，而 AgRP → 终纹前床核 (aBNST)vl 投射的激活与控制摄食的 AgRP → aBNSTdm 投射不同，介导 AgRP 神经元激活对 BAT-肌生长抑制素表达和胰岛素敏感性的影响。总的来说，我们的结果表明，小鼠中的 AgRP 神经元不仅诱导进食，还通过刺激 BAT 中肌肉相关基因的表达诱导胰岛素抵抗，揭示了这些神经元快速协调饥饿状态与葡萄糖稳态的机制。含有 AgRP 神经元的神经回路除了进食外，还通过刺激棕色脂肪组织中抑制葡萄糖摄取的肌肉相关基因的表达来诱导胰岛素抵抗，从而协调饥饿状态与葡萄糖稳态。
Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis. Neural circuits containing AgRP neurons coordinate hunger states with glucose homeostasis by inducing, in addition to eating, insulin resistance via stimulating expression of muscle-related genes in brown adipose tissue that inhibit glucose uptake.
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影响因子：
64.5
作者：
Dietrich MO;Zimmer MR;Bober J;Horvath TL
通讯作者：
Horvath TL
影响因子：
64.5
作者：
Gautron L;Elmquist JK;Williams KW
通讯作者：
Williams KW
DOI：
10.1016/j.biocel.2011.11.004
发表时间：
2012-02-01
影响因子：
4
作者：
Kim, Won Kon;Choi, Hye-Ryung;Lee, Sang Chul
通讯作者：
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影响因子：
29
作者：
Koenner, A. Christine;Janoschek, Ruth;Bruening, Jens C.
通讯作者：
Bruening, Jens C.
影响因子：
15.9
作者：
Krashes, Michael J.;Koda, Shuichi;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.