Contribution of microglial reaction to increased nociceptive responses in high-fat-diet (HFD)-induced obesity in male mice
Contribution of microglial reaction to increased nociceptive responses in high-fat-diet (HFD)-induced obesity in male mice
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小胶质细胞反应对高脂饮食（HFD）诱导的雄性小鼠肥胖伤害性反应增加的贡献
DOI：
10.1016/j.bbi.2019.05.026
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发表时间：
2019-08-01
影响因子：
15.1
通讯作者：
Fu, Kai-Yuan
中科院分区：
文献类型：
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作者：
Liang, Ya-Jing;Feng, Shi-Yang;Fu, Kai-Yuan
人口中肥胖症患病率的逐渐增加可能导致医疗保健成本和需求的增加。最近的研究揭示了疼痛和肥胖之间的正相关，尽管潜在的机制仍然未知。在这里，我们旨在阐明小胶质细胞在高脂肪饮食（HFD）诱导的雄性小鼠疼痛行为改变中的作用。我们发现，C57BL/6CR小鼠在HFD上表现出增强的脊髓小胶质细胞反应（细胞数量增加，p-p38和CD16/32的表达上调），肿瘤坏死因子-a (TNF-a) mRNA和脑源性神经营养因子（BDNF）蛋白表达增加，以及脊髓小胶质细胞向促炎表型极化。此外，我们发现使用PLX3397（一种选择性集落刺激因子-1受体（CSF1R）激酶抑制剂）消除hfd诱导的肥胖小鼠的小胶质细胞，脊髓炎症和异常疼痛超敏反应得以恢复。hld小鼠鞘内注射mac -1皂苷（一种皂苷偶联抗mac抗体）可减少小胶质细胞数量，减轻机械异常性痛和热痛觉过敏。这些结果表明，脊髓小胶质细胞的促炎功能与hfd诱导的肥胖小鼠异常疼痛超敏反应具有特殊的相关性。总之，我们的数据表明，HFD诱导了小胶质细胞的经典反应，其特征是p-38磷酸化增强和CD16/32表达增加，这可能在一定程度上促进了HFD诱导的肥胖小鼠的伤害性反应增加。
The progressive increase in the prevalence of obesity in the population can result in increased healthcare costs and demands. Recent studies have revealed a positive correlation between pain and obesity, although the underlying mechanisms still remain unknown. Here, we aimed to clarify the role of microglia in altered pain behaviors induced by high-fat diet (HFD) in male mice. We found that C57BL/6CR mice on HFD exhibited enhanced spinal microglial reaction (increased cell number and up-regulated expression of p-p38 and CD16/32), increased tumor necrosis factor-a (TNF-a) mRNA and brain-derived neurotrophic factor (BDNF) protein expression as well as a polarization of spinal microglial toward a pro-inflammatory phenotype. Moreover, we found that using PLX3397 (a selective colony-stimulating factor-1 receptor (CSF1R) kinase inhibitor) to eliminate microglia in HFD-induced obesity mice, inflammation in the spinal cord was rescued, as was abnormal pain hypersensitivity. Intrathecal injection of Mac-1-saporin (a saporin-conjugated anti-macl antibody) resulted in a decreased number of microglia and attenuated both mechanical allodynia and thermal hyperalgesia in HFD-fed mice. These results indicate that the pro-inflammatory functions of spinal microglia have a special relevance to abnormal pain hypersensitivity in HFD-induced obesity mice. In conclusion, our data suggest that HFD induces a classical reaction of microglia, characterized by an enhanced phosphorylation of p-38 and increased CD16/32 expression, which may in part contribute to increased nociceptive responses in HFD-induced obesity mice.