Chronic High-Fat Diet Consumption Followed by Lipopolysaccharide Challenge Induces Persistent and Long-Lasting Microglial Priming, Mediates Synaptic Elimination via Complement C1q, and Leads to Behavioral Abnormalities in Male Wistar Rats

IF 5.6 2区医学 Q1 PHYSIOLOGY

Acta Physiologica Pub Date : 2025-05-19 DOI:10.1111/apha.70060

Titikorn Chunchai, Hiranya Pintana, Chanon Kunasol, Patcharapong Pantiya, Busarin Arunsak, Sasiwan Kerdphoo, Wichwara Nawara, Suriphan Donchada, Nattayaporn Apaijai, Jirapas Sripetchwandee, Chanisa Thonusin, Nipon Chattipakorn, Siriporn C. Chattipakorn

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引用次数: 0

Abstract

Aim

Microglia exhibit innate immune memory, altering their responses to subsequent challenges. Consumption of high-fat diet (HFD) triggers innate immune responses, but the characteristics of HFD-induced microglial priming remain unclear. We aim to investigate how HFD-induced microglial priming, followed by a lipopolysaccharide (LPS) challenge, affects brain functions.

Methods

Male Wistar rats were divided into control, unprimed, and primed groups. The primed groups received either a single LPS injection (0.5 mg/kg, intraperitoneally) or HFD consumption for 4–8 weeks. Following the priming phase, all rats (except controls) were subjected to an LPS challenge with a 4- or 8-week interval. After 24 h of LPS challenge, cognition, anxiety-, and depressive-like behaviors were assessed. The brain and hippocampus were collected for further analysis.

Results

Both LPS- and 4-week HFD-primed groups, followed by LPS challenge, exhibited increased peripheral and brain oxidative stress, impaired neurogenesis, disrupted neurotransmitter balance, and altered glycolysis and Krebs cycle substrates. These changes also caused microglial morphological alterations, elevated C1q levels, and synaptic loss, which were associated with anxiety- and depressive-like behaviors, indicating that 4-week HFD consumption has a similar immune priming ability to a single dose of LPS injection. Extending HFD priming to 8 weeks exacerbated microglial and brain inflammation, synaptic loss, and behavioral deficits. Furthermore, prolonging the interval between priming and LPS challenge worsened inflammation and cognitive decline, suggesting the persistent effects of microglial priming.

Conclusions

HFD consumption persistently and time-dependently primes microglia similar to a single LPS injection, influencing immune responses and contributing to behavioral abnormalities.

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雄性Wistar大鼠慢性高脂肪饮食后脂多糖刺激诱导持续和持久的小胶质启动，通过补体C1q介导突触消除，并导致行为异常

目的小胶质细胞表现出先天免疫记忆，改变它们对后续挑战的反应。食用高脂肪饮食（HFD）会触发先天免疫反应，但HFD诱导的小胶质细胞启动的特征尚不清楚。我们的目的是研究hfd诱导的小胶质细胞启动，随后脂多糖（LPS）挑战，如何影响大脑功能。方法雄性Wistar大鼠分为对照组、未启动组和启动组。启动组接受单次LPS注射（0.5 mg/kg，腹腔注射）或消耗HFD，持续4-8周。在启动阶段之后，所有大鼠（除对照组外）都以4周或8周的间隔进行LPS刺激。LPS刺激24小时后，评估认知、焦虑和抑郁样行为。收集大脑和海马体作进一步分析。结果LPS组和4周hfd组均表现出外周和大脑氧化应激增加，神经发生受损，神经递质平衡被破坏，糖酵解和克雷布斯循环底物改变。这些变化还引起小胶质细胞形态学改变、C1q水平升高和突触丢失，这些与焦虑和抑郁样行为相关，表明4周食用HFD与单剂量LPS注射具有相似的免疫启动能力。HFD启动延长至8周会加重小胶质细胞和脑炎症、突触丧失和行为缺陷。此外，延长启动和LPS挑战之间的间隔会加重炎症和认知能力下降，这表明小胶质细胞启动的持续作用。结论持续且时间依赖性地消耗高脂食物会激活小胶质细胞，影响免疫反应并导致行为异常，类似于单次注射LPS。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Physiologica 医学-生理学

CiteScore

11.80

自引率

15.90%

发文量

182

审稿时长

4-8 weeks

期刊介绍： Acta Physiologica is an important forum for the publication of high quality original research in physiology and related areas by authors from all over the world. Acta Physiologica is a leading journal in human/translational physiology while promoting all aspects of the science of physiology. The journal publishes full length original articles on important new observations as well as reviews and commentaries.