High-fat diet feeding differentially affects the development of inflammation in the central nervous system.

High-fat diet feeding differentially affects the development of inflammation in the central nervous system.
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DOI:
10.1186/s12974-016-0666-8
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发表时间:
2016-08-26
影响因子:
9.3
通讯作者:
Muccioli GG
Muccioli GG
中科院分区:
医学1区
文献类型:
--
作者:
Guillemot-Legris O;Masquelier J;Everard A;Cani PD;Alhouayek M;Muccioli GG

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肥胖及其相关疾病正在成为许多国家的一个主要健康问题。由此产生的低度炎症不仅影响外周神经系统,也影响中枢神经系统。我们开始研究,以一种时间依赖的方式,高脂肪饮食对中枢神经系统不同区域的炎症性的影响。我们使用了饮食诱导的肥胖模型,并在几个时间点(1、2、4、6、8和16周)将喂食高脂肪饮食的一组小鼠与喂食标准饮食的对照组进行了比较。我们还使用HPLC-MS对中枢神经系统中的脂质进行了大规模分析,然后在星形胶质细胞和小胶质细胞的原代共培养中测试了感兴趣的脂质。我们在不同的时间点测量了小脑炎症张力的增加。然而,在第16周,我们证明了炎症音调在中枢神经系统的两个不同区域表现出显著差异,特别是小脑的增加,而高脂肪饮食小鼠的皮层与低脂喂养小鼠相比没有改变。我们的研究结果清楚地表明,中枢神经系统对高脂肪饮食的适应既依赖于区域,也依赖于时间。这两个区域的炎症性差异似乎涉及星形胶质细胞,而不涉及小胶质细胞。此外,大规模的脂质筛选与体外测试相结合,使我们能够确定三类脂质——磷脂酰肌醇、磷脂酰乙醇胺和溶血磷脂酰胆碱——以及棕榈酰乙醇酰胺,它们可能是导致炎症基调差异的原因。这项研究表明,由高脂肪饮食引起的炎症基调对中枢神经系统的不同区域没有类似的影响。此外,体外鉴定和测试的脂质显示出有趣的抗炎特性,可以进一步研究以更好地表征其活性及其在控制中枢神经系统炎症中的作用。本文的在线版本(doi:10.1186/s12974-016-0666-8)包含补充材料,可供授权用户使用。
Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet. We also performed a large-scale analysis of lipids in the central nervous system using HPLC-MS, and we then tested the lipids of interest on a primary co-culture of astrocytes and microglial cells. We measured an increase in the inflammatory tone in the cerebellum at the different time-points. However, at week 16, we evidenced that the inflammatory tone displayed significant differences in two different regions of the central nervous system, specifically an increase in the cerebellum and no modification in the cortex for high-fat diet mice when compared with chow-fed mice. Our results clearly suggest region-dependent as well as time-dependent adaptations of the central nervous system to the high-fat diet. The differences in inflammatory tone between the two regions considered seem to involve astrocytes but not microglial cells. Furthermore, a large-scale lipid screening coupled to ex vivo testing enabled us to identify three classes of lipids—phosphatidylinositols, phosphatidylethanolamines, and lysophosphatidylcholines—as well as palmitoylethanolamide, as potentially responsible for the difference in inflammatory tone. This study demonstrates that the inflammatory tone induced by a high-fat diet does not similarly affect distinct regions of the central nervous system. Moreover, the lipids identified and tested ex vivo showed interesting anti-inflammatory properties and could be further studied to better characterize their activity and their role in controlling inflammation in the central nervous system. The online version of this article (doi:10.1186/s12974-016-0666-8) contains supplementary material, which is available to authorized users.
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