Neudorf Helena, Sandilands Roderick E, Ursel Spencer, Shaba Hillary, Barg Darren, Tsusaka Takeshi, Moya-Garzón María Dolores, Vaz Erica, Schimweg Patricia, Goldberg Emily L, Long Jonathan Z, Krüger Karsten, Islam Hashim, Little Jonathan P
School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, BC, Canada.
Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.
iScience. 2025 Jun 11;28(7):112872. doi: 10.1016/j.isci.2025.112872. eCollection 2025 Jul 18.
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.
禁食和酮症在治疗肥胖相关的免疫代谢功能障碍方面正引起越来越多的关注。我们旨在：（1）描述人类对48小时禁食的全身和T细胞免疫代谢反应；（2）确定肥胖个体（O-BMI）和非肥胖个体（L-BMI）（每组n = 16）之间的反应是否存在差异。尽管全身脂肪氧化有相似程度的增加，但肥胖个体血液中β-羟基丁酸（BHB）、BHB-氨基酸共轭物和赖氨酸β-羟基丁酰化的增加却受到抑制。L-BMI组的T细胞上调了其脂肪氧化的相对能力，而O-BMI组则没有。即使在禁食后，O-BMI组的Th17细胞比例更高，分泌的白细胞介素-17（IL-17）更多。两组的CD8表达均下降，而只有L-BMI组的CD4表达下降。O-BMI组抗炎细胞因子与促炎细胞因子的平衡增加较少。总体而言，这些发现表明肥胖个体对禁食的全身和T细胞免疫代谢反应受到抑制。NCT05886738。
