Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice.
Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice.
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DOI：
10.1016/j.molmet.2014.10.001
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发表时间：
2015-01
影响因子：
8.1
通讯作者：
Ellacott KL
中科院分区：
文献类型：
--
作者：
Buckman LB;Thompson MM;Lippert RN;Blackwell TS;Yull FE;Ellacott KL
在体内平衡机制恢复能量摄入到等热量水平之前，给小鼠引入高脂肪饮食会导致一段时间的贪婪进食，称为贪食。急性高脂肪饮食暴饮暴食诱导啮齿动物下丘脑的星形胶质细胞激活，提示这些细胞在对饮食的稳态反应中可能起作用。本研究的目的是确定星形胶质细胞在高脂肪喂养的急性体内平衡反应中的生理作用。我们培育了一种多西环素诱导的星形胶质细胞中NFκB （NFκB）信号抑制的转基因小鼠模型，以确定NFκB介导的星形胶质细胞激活丧失对急性高脂肪贪食的影响。ELISA法测定大鼠下丘脑内侧基底区星形胶质细胞活化标志物、胶质纤维酸性蛋白（GFAP）和S100B水平。星形胶质细胞中NFκB信号的抑制阻止了高脂饮食诱导的星形胶质细胞的急性激活，并导致在引入饮食后的前24小时内热量摄入增加15% （P < 0.01）。这些数据揭示了星形胶质细胞在高脂肪喂养对食物摄入的急性生理调节中的一种新的稳态作用。
Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P < 0.01) in the first 24 h after introduction of the diet. These data reveal a novel homeostatic role for astrocytes in the acute physiologic regulation of food intake in response to high-fat feeding.