High-fat diet causes psychiatric disorders in mice by increasing Proteobacteria population
High-fat diet causes psychiatric disorders in mice by increasing Proteobacteria population
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DOI：
10.1016/j.neulet.2019.01.006
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发表时间：
2019-04-17
影响因子：
2.5
通讯作者：
Kim, Dong-Hyun
中科院分区：
文献类型：
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作者：
Jeong, Mi-Young;Jang, Hyo-Min;Kim, Dong-Hyun
高脂肪饮食（HFD）的过量摄入会导致肥胖，包括代谢综合征，扰乱肠道微生物群组成，引发结肠炎，并增加脂多糖（LPS）的血浆浓度。在本研究中，我们研究了肠道微生物群在小鼠高脂肪饮食诱导的精神障碍发生中的作用。给C57BL/6J雄性小鼠喂食高脂肪饮食9周导致其肥胖；通过Y型迷宫和新物体识别测试评估它们的记忆损伤，通过高架十字迷宫评估其焦虑样行为。高脂肪饮食的摄入抑制了海马体中脑源性神经营养因子（BDNF）的表达，并增加了血液中肿瘤坏死因子 -α（TNF -α）和脂多糖的水平。高脂肪饮食处理更强烈地增加了海马体中核因子 -κB（NF -κB）的活化以及离子钙结合衔接分子1（Iba1）阳性（小胶质细胞）细胞数量。此外，高脂肪饮食喂养增加了结肠中肿瘤坏死因子 -α的表达、髓过氧化物酶活性以及CD11b⁺/CD11c⁺细胞（巨噬细胞和树突状细胞）数量，改变了肠道微生物群组成，包括变形菌门数量的增加以及粪便中脂多糖水平的升高。与低脂饮食处理的小鼠相比，高脂肪饮食处理小鼠的粪便裂解物抑制了SH - SY5Y细胞中脑源性神经营养因子的表达和环磷腺苷效应元件结合蛋白（CREB）的磷酸化，并增加了BV - 2小胶质细胞中核因子 -κB的活化，而这些作用可通过抗脂多糖抗体处理而减弱。这些发现表明，高脂肪饮食的过量摄入可通过抑制海马体中脑源性神经营养因子的表达以及扰乱肠道微生物群组成，特别是变形菌门数量的增加和脂多糖的产生，同时导致肥胖和精神障碍。
The excessive intake of a high-fat diet (HFD) leads to obesity, including metabolic syndromes, disturbs gut microbiota composition, causes colitis, and increases the plasma concentration of lipopolysaccharide (LPS). In the present study, we examined the role of gut microbiota in the occurrence of HFD-induced psychiatric disorders in mice. C57BL/6 J male mice fed a HFD for 9 weeks were led to obesity; their memory impairment was assessed by the Y-maze and novel object recognition test, and anxiety-like behaviors by the elevated plus maze. The intake of a HFD suppressed brain-derived neurotrophic factor (BDNF) expression in the hippocampus and increased blood TNF-alpha and LPS levels. HFD treatment more potently increased NF-kappa B activation and Iba1(+) (microglial) cell populations in the hippocampus. Furthermore, HFD feeding increased TNF-alpha expression, myeloperoxidase activity, and CD11b(+)/CD11c(+) cell (macrophages and dendritic cells) populations in the colon and altered gut microbiota composition including increases in the Proteobacteria population, and increases in fecal LPS levels. The stool lysates of HFD-treated mice suppressed BDNF expression and CREB phosphorylation in SH-SY5Y cells and increased NF-kappa B activation in BV-2 microglial cells compared to those of low-fat diet-treated mice while these effects were attenuated by treatment with anti-LPS antibody. These findings suggest that excessive intake of HFD can simultaneously cause obesity and psychiatric disorders by suppressing hippocampal BDNF expression with the disturbance of gut microbiota composition, particularly the increase in Proteobacteria population and LPS production.