肥胖患者禁食后免疫代谢反应的改变

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-11 DOI:10.1016/j.isci.2025.112872

Helena Neudorf , Roderick E. Sandilands , Spencer Ursel , Hillary Shaba , Darren Barg , Takeshi Tsusaka , María Dolores Moya-Garzón , Erica Vaz , Patricia Schimweg , Emily L. Goldberg , Jonathan Z. Long , Karsten Krüger , Hashim Islam , Jonathan P. Little

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引用次数: 0

摘要

禁食和酮症在治疗肥胖相关的免疫代谢功能障碍方面越来越受到关注。我们的目的是(1)表征人类48小时禁食后的全身和T细胞免疫代谢反应；(2)确定（0 - bmi）和（L-BMI）肥胖个体之间的反应是否不同（每组n = 16）。尽管全身脂肪氧化也有类似的增加，但在肥胖人群中，血液中β-羟基丁酸酯（BHB）、BHB-氨基酸缀合物和赖氨酸β-羟基丁酸基化的增加却减弱了。来自L-BMI组的T细胞上调了脂肪氧化的相对能力，而O-BMI组则没有。O-BMI组的Th17细胞比例更高，即使在禁食后也会分泌更多的白细胞介素-17 （IL-17）。CD8表达在两组均下降，CD4表达仅在L-BMI组下降。抗-促炎细胞因子的平衡在0 - bmi组中增加较少。总的来说，这些发现表明，肥胖的人对禁食的全身和T细胞免疫代谢反应迟钝。NCT05886738。

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Altered immunometabolic response to fasting in humans living with obesity

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Altered immunometabolic response to fasting in humans living with obesity

Fasting and ketosis are gaining interest for treating obesity-related immunometabolic dysfunction. We aimed to (1) characterize systemic and T cell immunometabolic responses to a 48-h fast in humans and (2) determine if responses differed between individuals with (O-BMI) and without (L-BMI) obesity (n = 16 per group). Despite similar increases in systemic fat oxidation, increases in blood β-hydroxybutyrate (BHB), BHB-amino acid conjugates, and lysine β-hydroxybutyrylation were blunted in obesity. T cells from the L-BMI group upregulated their relative capacity for fat oxidation while the O-BMI group did not. The O-BMI group had a greater proportion of Th17 cells and secreted more interleukin-17 (IL-17), even after fasting. CD8 expression decreased in both groups and CD4 expression only decreased in the L-BMI group. The balance of anti-to pro-inflammatory cytokines increased less in the O-BMI group. Collectively, these findings show that humans living with obesity have a blunted systemic and T cell immunometabolic response to fasting. NCT05886738.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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