Ketone bodies rescue T cell impairments induced by low glucose availability.

IF 4.1 2区 医学 Q2 NUTRITION & DIETETICS European Journal of Nutrition Pub Date : 2024-10-01 Epub Date: 2024-08-06 DOI:10.1007/s00394-024-03469-w
Arianna Ferrari, Jessica Filoni, Carla Di Dedda, Lorenzo Piemonti, Paolo Monti
{"title":"Ketone bodies rescue T cell impairments induced by low glucose availability.","authors":"Arianna Ferrari, Jessica Filoni, Carla Di Dedda, Lorenzo Piemonti, Paolo Monti","doi":"10.1007/s00394-024-03469-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Ketogenic diets are proposed as a therapeutic approach for type 1 and type 2 diabetes due to their low glucose intake. However, their potential effects on the immune system need investigation. This study aims to explore how glucose concentration and beta-hydroxybutyrate (BHB) impact T cell phenotype, metabolism, and function, with a focus on systemic inflammatory response (T2D) and autoimmunity (T1D).</p><p><strong>Methods: </strong>T cells from healthy donors were cultured in vitro under varying glucose concentrations with or without BHB. Flow cytometry was employed to analyze changes in T cell phenotype, while proliferation was evaluated through a CFSE dilution assay. Additionally, we used a novel flow cytometry method allowing a direct assessment of T cell metabolism.</p><p><strong>Results: </strong>Culturing T cells in low glucose concentrations revealed their dependency on glucose metabolism, leading to reduced proliferation rates, overexpression of exhaustion markers and increased susceptibility to Treg suppression and the influence of immune-modulating drugs such as rapamycin, FK506, and MMF. Notably, T cells cultured in low glucose concentrations increased the expression of BDH1 to utilize BHB as an alternative fuel source. Finally, the addition of BHB to the culture effectively rescued T cell impairments caused by insufficient glucose levels.</p><p><strong>Conclusions: </strong>T cells display limited capacity to adapt to low glucose levels, resulting in profound functional impairment. However, T cell functions can be efficiently recovered by the presence of 2mM BHB.</p>","PeriodicalId":12030,"journal":{"name":"European Journal of Nutrition","volume":" ","pages":"2815-2825"},"PeriodicalIF":4.1000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00394-024-03469-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose: Ketogenic diets are proposed as a therapeutic approach for type 1 and type 2 diabetes due to their low glucose intake. However, their potential effects on the immune system need investigation. This study aims to explore how glucose concentration and beta-hydroxybutyrate (BHB) impact T cell phenotype, metabolism, and function, with a focus on systemic inflammatory response (T2D) and autoimmunity (T1D).

Methods: T cells from healthy donors were cultured in vitro under varying glucose concentrations with or without BHB. Flow cytometry was employed to analyze changes in T cell phenotype, while proliferation was evaluated through a CFSE dilution assay. Additionally, we used a novel flow cytometry method allowing a direct assessment of T cell metabolism.

Results: Culturing T cells in low glucose concentrations revealed their dependency on glucose metabolism, leading to reduced proliferation rates, overexpression of exhaustion markers and increased susceptibility to Treg suppression and the influence of immune-modulating drugs such as rapamycin, FK506, and MMF. Notably, T cells cultured in low glucose concentrations increased the expression of BDH1 to utilize BHB as an alternative fuel source. Finally, the addition of BHB to the culture effectively rescued T cell impairments caused by insufficient glucose levels.

Conclusions: T cells display limited capacity to adapt to low glucose levels, resulting in profound functional impairment. However, T cell functions can be efficiently recovered by the presence of 2mM BHB.

Abstract Image

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
酮体可挽救低葡萄糖供应引起的 T 细胞损伤。
目的:生酮饮食因其葡萄糖摄入量低而被建议作为 1 型和 2 型糖尿病的治疗方法。然而,它们对免疫系统的潜在影响还需要研究。本研究旨在探讨葡萄糖浓度和β-羟丁酸(BHB)如何影响 T 细胞表型、代谢和功能,重点是全身炎症反应(T2D)和自身免疫(T1D):方法:在有或没有 BHB 的不同葡萄糖浓度条件下体外培养健康供体的 T 细胞。流式细胞术用于分析 T 细胞表型的变化,而增殖则通过 CFSE 稀释试验进行评估。此外,我们还使用了一种新型流式细胞术方法,可直接评估 T 细胞的新陈代谢:结果:在低浓度葡萄糖中培养 T 细胞显示了它们对葡萄糖代谢的依赖性,导致增殖率降低、衰竭标记物过度表达、对 Treg 抑制的易感性增加以及雷帕霉素、FK506 和 MMF 等免疫调节药物的影响。值得注意的是,在低浓度葡萄糖中培养的 T 细胞增加了 BDH1 的表达,以利用 BHB 作为替代燃料来源。最后,在培养过程中添加 BHB 能有效缓解葡萄糖水平不足对 T 细胞造成的损伤:结论:T 细胞对低葡萄糖水平的适应能力有限,导致其功能严重受损。结论:T 细胞对低葡萄糖水平的适应能力有限,导致其功能严重受损。然而,2mM BHB 的存在可有效恢复 T 细胞的功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
10.20
自引率
2.00%
发文量
295
审稿时长
6 months
期刊介绍: The European Journal of Nutrition publishes original papers, reviews, and short communications in the nutritional sciences. The manuscripts submitted to the European Journal of Nutrition should have their major focus on the impact of nutrients and non-nutrients on immunology and inflammation, gene expression, metabolism, chronic diseases, or carcinogenesis, or a major focus on epidemiology, including intervention studies with healthy subjects and with patients, biofunctionality of food and food components, or the impact of diet on the environment.
期刊最新文献
Association between magnesium and vitamin D status in adults with high prevalence of vitamin D deficiency and insufficiency. Higher intake energy, protein, and polyunsaturated fatty acids at dinner versus breakfast increase the risk of hyperhomocysteinemia among adults in the USA. Isothiocyanates induce autophagy and inhibit protein synthesis in primary cells via modulation of AMPK-mTORC1-S6K1 signaling pathway, and protect against mutant huntingtin aggregation. Chrononutrition behaviors and cardiometabolic risk in adolescence: an ecological momentary assessment study. Joint association of anti-inflammatory diet and vigorous leisure-time physical activity on all-cause and cardiovascular disease mortality in U.S. adults: findings from NHANES, 2007-2014.
×
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