Dorsal vagal complex and hypothalamic glia differentially respond to leptin and energy balance dysregulation.
Dorsal vagal complex and hypothalamic glia differentially respond to leptin and energy balance dysregulation.
复制标题
背侧迷走神经复合体和下丘脑神经胶质细胞对瘦素和能量平衡失调的反应不同。
DOI：
10.1038/s41398-020-0767-0
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发表时间：
2020
影响因子：
6.8
通讯作者：
Hayes,MatthewR
中科院分区：
文献类型：
--
作者：
Stein,LaurenM;Lhamo,Rinzin;Cao,Anh;Workinger,Jayme;Tinsley,Ian;Doyle,RobertP;Grill,HarveyJ;Hermann,GerlindaE;Rogers,RichardC;Hayes,MatthewR
先前的研究确定了下丘脑胶质细胞在能量平衡调节中的作用;然而，狭窄的下丘脑焦点提供了对整个大脑的胶质细胞如何响应和调节能量稳态的不完全理解。我们研究了背侧迷走神经复合体（DVC）中胶质细胞对脂肪因子瘦素和高脂饮食诱导的肥胖的反应。DVC星形胶质细胞功能性表达瘦素受体;体内药理学研究表明，DVC星形胶质细胞部分介导瘦素在瘦大鼠中的厌食作用，而不是饮食诱导的肥胖大鼠。离体钙成像表明，这些变化与较低比例的瘦素反应细胞在DVC的肥胖与瘦动物。最后，我们研究了DVC小胶质细胞和星形胶质细胞对瘦素和体内能量平衡失调的反应：肥胖降低了DVC星形胶质细胞增生，而Zucker大鼠中缺乏瘦素信号传导与DVC中广泛的星形胶质细胞增生和下丘脑微小和星形胶质细胞增生减少相关。这些数据揭示了一种新的功能异质性的星形胶质细胞在不同的大脑核团的相关瘦素信号和能量平衡调节。
Previous studies identify a role for hypothalamic glia in energy balance regulation; however, a narrow hypothalamic focus provides an incomplete understanding of how glia throughout the brain respond to and regulate energy homeostasis. We examined the responses of glia in the dorsal vagal complex (DVC) to the adipokine leptin and high fat diet-induced obesity. DVC astrocytes functionally express the leptin receptor; in vivo pharmacological studies suggest that DVC astrocytes partly mediate the anorectic effects of leptin in lean but not diet-induced obese rats. Ex vivo calcium imaging indicated that these changes were related to a lower proportion of leptin-responsive cells in the DVC of obese versus lean animals. Finally, we investigated DVC microglia and astroglia responses to leptin and energy balance dysregulation in vivo: obesity decreased DVC astrogliosis, whereas the absence of leptin signaling in Zucker rats was associated with extensive astrogliosis in the DVC and decreased hypothalamic micro- and astrogliosis. These data uncover a novel functional heterogeneity of astrocytes in different brain nuclei of relevance to leptin signaling and energy balance regulation.