Wang Yuping, Hsuchou Hung, He Yi, Kastin Abba J, Pan Weihong
Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA.
Biopotentials Sleep Center, 8032 Summa Ave, Ste A, Baton Rouge, LA, 70809, USA.
J Mol Neurosci. 2015 Aug;56(4):829-839. doi: 10.1007/s12031-015-0518-5. Epub 2015 Feb 17.
To test the hypothesis that astrocytic leptin signaling induces an overall potentiation of the neuronal response to leptin, we generated a new line of astrocyte-specific leptin receptor knockout (ALKO-Δ1) mice in which no leptin receptor is expressed in astrocytes. Corresponding to cell-specific Cre recombinase expression in hypothalamic astrocytes but not neurons, this new strain of ALKO mice had attenuated pSTAT3 signaling in the arcuate nucleus of the hypothalamus 30 min after intracerebroventricular delivery of leptin. In response to high-fat diet for 2 months, the ALKO mice showed a greater increase of percent fat and blood leptin concentration. This coincided with a mild reactive gliosis in the hypothalamus. Overall, the absence of leptin receptors in astrocytes attenuated hypothalamic pSTAT3 signaling, induced a mild reactive morphology, and promoted the development of diet-induced obesity. We conclude that leptin signaling in astrocytes is essential for the homeostasis of neuroendocrine regulation in obesity.
为了验证星形胶质细胞的瘦素信号传导会诱导神经元对瘦素反应的整体增强这一假设，我们培育了一种新的星形胶质细胞特异性瘦素受体敲除（ALKO-Δ1）小鼠品系，其中星形胶质细胞中不表达瘦素受体。与下丘脑星形胶质细胞而非神经元中细胞特异性Cre重组酶的表达相对应，这种新的ALKO小鼠品系在脑室内注射瘦素30分钟后，下丘脑弓状核中的pSTAT3信号传导减弱。在高脂饮食2个月后，ALKO小鼠的脂肪百分比和血液瘦素浓度有更大幅度的增加。这与下丘脑中轻度的反应性胶质增生相吻合。总体而言，星形胶质细胞中缺乏瘦素受体会减弱下丘脑pSTAT3信号传导，诱导轻度的反应性形态，并促进饮食诱导的肥胖症的发展。我们得出结论，星形胶质细胞中的瘦素信号传导对于肥胖症中神经内分泌调节的稳态至关重要。
