生命早期的肥胖环境整合了免疫代谢和表观遗传特征,对神经炎症起着调节作用

IF 3.7 Q2 IMMUNOLOGY Brain, behavior, & immunity - health Pub Date : 2024-10-02 DOI:10.1016/j.bbih.2024.100879
{"title":"生命早期的肥胖环境整合了免疫代谢和表观遗传特征,对神经炎症起着调节作用","authors":"","doi":"10.1016/j.bbih.2024.100879","DOIUrl":null,"url":null,"abstract":"<div><div>Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS). Effects were assessed using behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), 16S rRNA gene sequencing for gut microbiome profiling, hippocampal microglia analysis, and targeted gene methylation. Parallel experiments on human microglia cells (HMC3) examined how palmitic acid influences cortisol-related inflammatory responses.</div><div>Rats exposed to WD and PSS exhibited deficits in sociability, increased fear/anxiety-like behaviors, food consumption, and body weight. WD/PSS altered hippocampal microstructure (subiculum, CA1, dentate gyrus), and microbiome analysis showed a reduced abundance of members of the phylum <em>Firmicutes</em>. WD/PSS synergistically promoted neuroinflammatory changes in hippocampal microglia, linked with microbiome shifts and altered <em>Fkbp5</em> expression/methylation. In HMC3, palmitate disrupted cortisol responses, affecting morphology, phagocytic markers, and cytokine release, partially mediated by FKBP5.</div><div>This study identifies gene-environment interactions that influence microglia biology and may contribute to the connection between childhood obesity and stress-related psychopathology later in life.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation\",\"authors\":\"\",\"doi\":\"10.1016/j.bbih.2024.100879\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS). Effects were assessed using behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), 16S rRNA gene sequencing for gut microbiome profiling, hippocampal microglia analysis, and targeted gene methylation. Parallel experiments on human microglia cells (HMC3) examined how palmitic acid influences cortisol-related inflammatory responses.</div><div>Rats exposed to WD and PSS exhibited deficits in sociability, increased fear/anxiety-like behaviors, food consumption, and body weight. WD/PSS altered hippocampal microstructure (subiculum, CA1, dentate gyrus), and microbiome analysis showed a reduced abundance of members of the phylum <em>Firmicutes</em>. WD/PSS synergistically promoted neuroinflammatory changes in hippocampal microglia, linked with microbiome shifts and altered <em>Fkbp5</em> expression/methylation. In HMC3, palmitate disrupted cortisol responses, affecting morphology, phagocytic markers, and cytokine release, partially mediated by FKBP5.</div><div>This study identifies gene-environment interactions that influence microglia biology and may contribute to the connection between childhood obesity and stress-related psychopathology later in life.</div></div>\",\"PeriodicalId\":72454,\"journal\":{\"name\":\"Brain, behavior, & immunity - health\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, behavior, & immunity - health\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666354624001571\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, behavior, & immunity - health","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666354624001571","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

儿童期超重/肥胖与压力相关的精神病理学有关,但人们对儿童期肥胖与压力易感性之间的联系途径却知之甚少。我们采用了一种系统生物学方法,对 62 只青少年 Lewis 大鼠喂食类似西方的高饱和脂肪饮食(WD,41% 千卡热量来自脂肪)或对照饮食(CD,13% 千卡热量来自脂肪)。其中一部分大鼠接受了为期 31 天的捕食者暴露和社会不稳定性(PSS)模型试验。通过行为测试、DTI(弥散张量成像)、NODDI(神经元定向弥散和密度成像)、16S rRNA 基因测序(用于肠道微生物组分析)、海马小胶质细胞分析和靶向基因甲基化来评估其影响。在人类小胶质细胞(HMC3)上进行的平行实验研究了棕榈酸如何影响与皮质醇相关的炎症反应。暴露于 WD 和 PSS 的大鼠表现出社交障碍、恐惧/焦虑样行为增加、食量和体重增加。WD/PSS改变了海马的微观结构(子网、CA1、齿状回),微生物组分析表明,固着菌门成员的丰度降低。WD/PSS 协同促进了海马小胶质细胞的神经炎症变化,这与微生物组的变化和 Fkbp5 表达/甲基化的改变有关。在 HMC3 中,棕榈酸酯会扰乱皮质醇反应,影响形态、吞噬标记物和细胞因子释放,部分由 FKBP5 介导。这项研究确定了影响小胶质细胞生物学的基因-环境相互作用,并可能有助于研究儿童肥胖与日后生活中与压力相关的精神病理学之间的联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation
Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS). Effects were assessed using behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), 16S rRNA gene sequencing for gut microbiome profiling, hippocampal microglia analysis, and targeted gene methylation. Parallel experiments on human microglia cells (HMC3) examined how palmitic acid influences cortisol-related inflammatory responses.
Rats exposed to WD and PSS exhibited deficits in sociability, increased fear/anxiety-like behaviors, food consumption, and body weight. WD/PSS altered hippocampal microstructure (subiculum, CA1, dentate gyrus), and microbiome analysis showed a reduced abundance of members of the phylum Firmicutes. WD/PSS synergistically promoted neuroinflammatory changes in hippocampal microglia, linked with microbiome shifts and altered Fkbp5 expression/methylation. In HMC3, palmitate disrupted cortisol responses, affecting morphology, phagocytic markers, and cytokine release, partially mediated by FKBP5.
This study identifies gene-environment interactions that influence microglia biology and may contribute to the connection between childhood obesity and stress-related psychopathology later in life.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
自引率
0.00%
发文量
0
审稿时长
97 days
期刊最新文献
BDNF methylation associated with stress in women: Novel insights in epigenetics and inflammation Repurposing doxycycline for Alzheimer's treatment: Challenges from a nano-based drug delivery perspective Associations between uric acid and depressive symptoms, and the mediating role of immunoinflammatory: Findings from rural older adults Clinical features and predictive nomogram for fatigue sequelae in non-severe patients infected with SARS-CoV-2 Omicron variant in Shanghai, China Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1