Hypothalamic astrocytes control systemic glucose metabolism and energy balance.
Hypothalamic astrocytes control systemic glucose metabolism and energy balance.
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DOI：
10.1016/j.cmet.2022.09.002
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发表时间：
2022-10-04
期刊：
影响因子：
29
通讯作者：
Luquet, Serge H.
中科院分区：
文献类型：
--
作者：
Chao, Daniela Herrera Moro;Kirchner, Matthew K.;Pham, Cuong;Foppen, Ewout;Denis, Raphael G. P.;Castel, Julien;Morel, Chloe;Montalban, Enrica;Hassouna, Rim;Bui, Linh-Chi;Renault, Justine;Mouffle, Christine;Garcia-Caceres, Cristina;Tschop, Matthias H.;Li, Dongdong;Martin, Claire;Stern, Javier E.;Luquet, Serge H.
下丘脑是控制能量平衡的关键。然而，针对下丘脑神经元的策略未能提供治疗大多数代谢性疾病的可行选择。相反，星形胶质细胞在全身代谢控制中的作用在很大程度上仍未被探索。在这里，我们表明肥胖促进下丘脑星形胶质细胞活性的解剖限制性重塑。在下丘脑室旁核（PVN）中，星形胶质细胞的化学发生操纵导致对邻近神经元活动、自主神经流出、葡萄糖代谢和能量平衡的双向控制。这个过程涉及星形细胞控制周围谷氨酸水平的机制，这在肥胖中变得有缺陷。PVN星形胶质细胞Ca2+信号的阳性或阴性化学发生操作分别恶化或改善饮食诱导的肥胖小鼠的代谢状态。总的来说，这些发现突出了星形胶质细胞在直接控制全身代谢中的作用，并提出了抗肥胖策略的潜在靶点。Herrera Moro Chao等人的研究表明，肥胖促进了下丘脑星形胶质细胞活性的解剖限制性重塑。在下丘脑室旁核（PVN）中，星形胶质细胞的化学发生操纵通过控制周围谷氨酸水平双向控制邻近神经元活动、自主神经流出、葡萄糖代谢和能量平衡。
The hypothalamus is key in the control of energy balance. However, strategies targeting hypothalamic neurons have failed to provide viable options to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored. Here we show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus (PVN) of the hypothalamus, chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism and energy balance. This process recruits a mechanism involving the astrocytic control of ambient glutamate levels, which becomes defective in obesity. Positive or negative chemogenetic manipulation of PVN astrocyte Ca2+ signals respectively worsens or improves metabolic status of diet-induced obese mice. Collectively, these findings highlight a yet unappreciated role for astrocytes in the direct control of systemic metabolism and suggest potential targets for anti-obesity strategy. Herrera Moro Chao et al. show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus of the hypothalamus (PVN), chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism and energy balance through the control of ambient glutamate levels.
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影响因子：
64.5
作者：
García-Cáceres C;Quarta C;Varela L;Gao Y;Gruber T;Legutko B;Jastroch M;Johansson P;Ninkovic J;Yi CX;Le Thuc O;Szigeti-Buck K;Cai W;Meyer CW;Pfluger PT;Fernandez AM;Luquet S;Woods SC;Torres-Alemán I;Kahn CR;Götz M;Horvath TL;Tschöp MH
通讯作者：
Tschöp MH
影响因子：
5.5
作者：
Fleming, Tiffany M.;Scott, Victoria;Stern, Javier E.
通讯作者：
Stern, Javier E.
DOI：
10.1016/j.ecl.2012.11.003
发表时间：
2013-03-01
影响因子：
4.5
作者：
Garcia-Caceres, Cristina;Yi, Chun-Xia;Tschoep, Matthias H.
通讯作者：
Tschoep, Matthias H.
影响因子：
64.8
作者：
Bezzi, P;Carmignoto, G;Volterra, A
通讯作者：
Volterra, A
影响因子：
2.5
作者：
Buckman, Laura B.;Thompson, Misty M.;Moreno, Heidi N.;Ellacott, Kate L. J.
通讯作者：
Ellacott, Kate L. J.