Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Department of Chemistry, Syracuse University, Syracuse, NY, USA.
Transl Psychiatry. 2020 Mar 9;10(1):90. doi: 10.1038/s41398-020-0767-0.
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.
先前的研究确定了下丘脑神经胶质在能量平衡调节中的作用；然而，狭隘的下丘脑焦点提供了对大脑中神经胶质如何响应和调节能量稳态的不完整理解。我们研究了背侧迷走神经复合体 (DVC) 中神经胶质对脂肪因子瘦素和高脂肪饮食诱导肥胖的反应。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但不是饮食诱导肥胖大鼠中的厌食作用。离体钙成像表明，这些变化与肥胖动物 DVC 中瘦素反应细胞的比例较低有关。最后，我们研究了 DVC 小胶质细胞和星形胶质细胞对瘦素和能量平衡失调的体内反应：肥胖会降低 DVC 星形胶质细胞增生，而 Zucker 大鼠中瘦素信号缺失与 DVC 中广泛的星形胶质细胞增生以及下丘脑小胶质细胞和星形胶质细胞增生减少有关。这些数据揭示了与瘦素信号和能量平衡调节相关的不同脑核中星形胶质细胞的新的功能异质性。
