Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
Department of Cell Biology and Anatomy, Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
BMC Neurosci. 2019 Jul 10;20(1):33. doi: 10.1186/s12868-019-0516-6.
Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals. However, the effect of chronic HFD feeding on oligodendrocytes (OLGs), a myelin-producing glial population in the central nervous system (CNS), remains unclear. In this study, we used 8-week old male C57BL/6 mice fed by HFD for 3-6 months to induce chronic obesity.
The transmission electron microscopy imaging analysis showed that the integrity of hypothalamic myelin was disrupted after HFD feeding for 4 and 6 months. Moreover, the accumulation of Iba1-microglia with an amoeboid hypertrophic form was continually observed in arcuate nucleus of HFD-fed mice during the entire feeding time period. Interleukin-33 (IL-33), a tissue alarmin upon injury to the CNS, was detected with an increased level in hypothalamus after HFD feeding for 3 and 4 months. Furthermore, the in vitro study indicated that exposure of mature OLGs to IL-33 impaired OLG cell structure along with a decline in the expression of myelin basic protein.
Altogether, our findings demonstrate that chronic HFD feeding triggers hypothalamic myelin disruption in accompany with IL-33 upregulation and prolonged microglial activation in hypothalamus. Given that the addition of exogenous IL-33 was harmful for the maturation of OLGs, an increase in IL-33 by chronic HFD feeding might contribute to the induction of hypothalamic myelin disruption.
在啮齿动物模型或肥胖个体中，摄入高脂肪饮食（HFD）后会发生下丘脑炎症，包括星形胶质细胞增生和小胶质细胞活化。然而，慢性 HFD 喂养对少突胶质细胞（OLGs）的影响，即中枢神经系统（CNS）中产生髓鞘的神经胶质细胞群体，仍不清楚。在这项研究中，我们使用 8 周龄雄性 C57BL/6 小鼠进行 HFD 喂养 3-6 个月以诱导慢性肥胖。
透射电子显微镜成像分析显示，HFD 喂养 4 个月和 6 个月后，下丘脑髓鞘的完整性被破坏。此外，在整个喂养期间，HFD 喂养小鼠弓状核中持续观察到 Iba1-小胶质细胞的积累，呈阿米巴样肥大形式。白细胞介素 33（IL-33）是中枢神经系统损伤时的组织警报素，在 HFD 喂养 3 个月和 4 个月后，下丘脑的检测水平升高。此外，体外研究表明，IL-33 暴露于成熟的 OLG 会损害 OLG 细胞结构，同时髓鞘碱性蛋白的表达下降。
总之，我们的研究结果表明，慢性 HFD 喂养会引发下丘脑髓鞘破坏，同时伴有下丘脑 IL-33 上调和小胶质细胞激活延长。鉴于外源性 IL-33 对 OLG 成熟有害，慢性 HFD 喂养引起的 IL-33 增加可能有助于诱导下丘脑髓鞘破坏。
