Profound weight loss induces reactive astrogliosis in the arcuate nucleus of obese mice
Profound weight loss induces reactive astrogliosis in the arcuate nucleus of obese mice
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DOI：
10.1016/j.molmet.2019.03.009
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发表时间：
2019-06-01
影响因子：
8.1
通讯作者：
Pfluger, Paul T.
中科院分区：
文献类型：
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作者：
Harrison, Luke;Pfuhlmann, Katrin;Pfluger, Paul T.
目的：肥胖与下丘脑的炎症样状态有关，其主要特征是星形胶质细胞和小胶质细胞的反应性神经胶质增生（RG）。在这里，我们使用两种饮食模型或药物治疗，评估了在高脂饮食 (HFD) 诱导的肥胖背景下，轻度和剧烈体重减轻对 RG 的影响。方法：我们对 HFD 诱导的肥胖 (DIO) 雄性 C57BU6J 小鼠进行减重干预，包括改用标准食物、热量限制 (CR) 或使用 Glp1 受体激动剂 Exendin-4 (EX4) 治疗。 RG 的严重程度是通过基于神经胶质原纤维酸性蛋白的荧光强度、离子钙结合接头分子 1 阳性 (Iba1)、细胞数量和形态特征的顺序评分系统来评估的。结果：与之前的报道相反，与食物对照组相比，长期 HFD 喂养的 DIO 小鼠的小胶质细胞或星形细胞 RG 没有差异。此外，轻度或深度体重减轻对小胶质细胞 RG 没有影响。然而，与食物喂养的动物相比，CR 和 EX4 组的星形胶质细胞 RG 增加，并且与体重减轻密切相关。 CR 或 EX4 的显着体重减轻进一步与循环非酯化游离脂肪酸水平增加有关。结论：总体而言，我们的数据表明，在长期肥胖状态下，星形胶质细胞和小胶质细胞 RG 与年龄匹配的食物对照中观察到的情况没有差异。尽管如此，严重的急性体重减轻可能会导致下丘脑弓状核中的星形胶质细胞 RG，这可能是由于循环 NEFA 的增加所致。这表明星形胶质细胞可能感知饮食环境和体重的急剧变化。 (C) 2019 年作者。由爱思唯尔有限公司出版。
Objective: Obesity has been linked to an inflammation like state in the hypothalamus, mainly characterized by reactive gliosis (RG) of astrocytes and microglia. Here, using two diet models or pharmacological treatment, we assessed the effects of mild and drastic weight loss on RG, in the context of high-fat diet (HFD) induced obesity.Methods: We subjected HFD-induced obese (DIO) male C57BU6J mice to a weight loss intervention with a switch to standard chow, calorie restriction (CR), or treatment with the Glp1 receptor agonist Exendin-4 (EX4). The severity of RG was estimated by an ordinal scoring system based on fluorescence intensities of glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1 positive (Iba1), cell numbers, and morphological characteristics.Results: In contrast to previous reports, DIO mice fed chronically with HFD showed no differences in microglial or astrocytic RG, compared to chow controls. Moreover, mild or profound weight loss had no impact on microglial RG. However, astrocyte RG was increased in CR and EX4 groups compared to chow fed animals and strongly correlated to body weight loss. Profound weight loss by either CR or EX4 was further linked to increased levels of circulating non-esterified free fatty acids.Conclusions: Overall, our data demonstrate that in a chronically obese state, astrocyte and microglial RG is indifferent from that observed in age-matched chow controls. Nonetheless, profound acute weight loss can induce astrocyte RG in the hypothalamic arcuate nucleus, possibly due to increased circulating NEFAs. This suggests that astrocytes may sense acute changes to both the dietary environment and body weight. (C) 2019 The Authors. Published by Elsevier GmbH.