Department of Organ Anatomy, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Mol Neurobiol. 2018 Dec;55(12):9016-9028. doi: 10.1007/s12035-018-1033-9. Epub 2018 Apr 6.
The hypothalamus is involved in the regulation of food intake and energy homeostasis. The arcuate nucleus (ARC) and median eminence (ME) are the primary hypothalamic sites that sense leptin and nutrients in the blood, thereby mediating food intake. Recently, studies demonstrating a role for non-neuronal cell types, including astrocytes and tanycytes, in these regulatory processes have begun to emerge. However, the molecular mechanisms involved in these activities remain largely unknown. In this study, we examined in detail the localization of fatty acid-binding protein 7 (FABP7) in the hypothalamic ARC and sought to determine its role in the hypothalamus. We performed a phenotypic analysis of diet-induced FABP7 knockout (KO) obese mice and of FABP7 KO mice treated with a single leptin injection. Immunohistochemistry revealed that FABP7 cells are NG2 or GFAP in the ARC and ME. In mice fed a high-fat diet, weight gain and food intake were lower in FABP7 KO mice than in wild-type (WT) mice. FABP7 KO mice also had lower food intake and weight gain after a single injection of leptin, and we consistently confirmed that the number of pSTAT3 cells in the ARC indicated that the leptin-induced activation of neurons was significantly more frequent in FABP7 KO mice than in WT mice. In FABP7 KO mice-derived primary astrocyte cultures, the level of ERK phosphorylation was lower after leptin treatment. Collectively, these results indicate that in hypothalamic astrocytes, FABP7 might be involved in sensing neuronal leptin via glia-mediated mechanisms and plays a pivotal role in controlling systemic energy homeostasis.
下丘脑参与调节食物摄入和能量平衡。弓状核（ARC）和正中隆起（ME）是主要的下丘脑部位，能够感知血液中的瘦素和营养物质，从而调节食物摄入。最近，研究表明非神经元细胞类型，包括星形胶质细胞和室管膜细胞，在这些调节过程中起作用。然而，这些活动所涉及的分子机制在很大程度上仍然未知。在这项研究中，我们详细研究了脂肪酸结合蛋白 7（FABP7）在下丘脑 ARC 中的定位，并试图确定其在下丘脑中的作用。我们对饮食诱导的 FABP7 敲除（KO）肥胖小鼠和接受单次瘦素注射的 FABP7 KO 小鼠进行了表型分析。免疫组织化学显示，FABP7 细胞在 ARC 和 ME 中是 NG2 或 GFAP。在高脂肪饮食喂养的小鼠中，FABP7 KO 小鼠的体重增加和食物摄入低于野生型（WT）小鼠。FABP7 KO 小鼠在单次注射瘦素后，食物摄入和体重增加也较低，我们一致证实 ARC 中 pSTAT3 细胞的数量表明，瘦素诱导的神经元激活在 FABP7 KO 小鼠中比在 WT 小鼠中更为频繁。在 FABP7 KO 小鼠衍生的原代星形胶质细胞培养物中，瘦素处理后 ERK 磷酸化水平较低。总之，这些结果表明，在下丘脑星形胶质细胞中，FABP7 可能通过胶质细胞介导的机制参与感知神经元瘦素，并在控制全身能量平衡中发挥关键作用。
