抑制基础IL-6活性促进人类在禁食和餐后状态下皮下脂肪潴留。

IF 11.7 1区 医学 Q1 CELL BIOLOGY
Beckey Trinh, Signe Johanne Rasmussen, Mathilde Ehnhuus Brøgger-Jensen, Christoph Andreas Engelhard, Anton Lund, Ana Rita Tavanez, Alexandra Vassilieva, Susanne Janum, Ulrik Winning Iepsen, Bente Kiens, Kirsten Møller, Bente Klarlund Pedersen, Gerrit Van Hall, Helga Ellingsgaard
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引用次数: 0

摘要

白细胞介素6 (IL-6)敲除小鼠和人用IL-6受体阻断治疗增加脂肪组织质量。本研究探讨了基础IL-6活性(静息IL-6水平)是否影响空腹和餐后状态下的脂肪储存。使用稳定同位素示踪技术和IL-6受体阻断tocilizumab,我们检查人类脂肪动力学。阻断基础IL-6活性可减少空腹全身脂肪分解,降低激素敏感脂肪酶(HSL)磷酸化和脂肪组织中的脂肪酸释放,并损害餐后腿部脂肪酸摄取。这些结果表明,骨骼肌中脂肪酸摄取和氧化减少,脂肪组织中脂肪酸滞留增加,这可能是在缺乏IL-6活性的情况下肥胖增加的原因。此外,IL-6阻断增加了食物来源的脂肪酸逃逸到血液中。这是否影响脂肪酸储存和脂肪毒性在其他组织有待进一步研究。本研究已在ClinicalTrials.gov注册(NCT04687540)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states.

Interleukin-6 (IL-6) knockout mice and humans treated with IL-6 receptor blockade gain adipose tissue mass. This study investigates whether basal IL-6 activity (resting IL-6 levels) influences fat storage during fasting and postprandial states. Using stable-isotope tracer techniques and IL-6 receptor blockade with tocilizumab, we examine fat kinetics in humans. Blocking basal IL-6 activity reduces fasting whole-body lipolysis, decreases hormone-sensitive lipase (HSL) phosphorylation and fatty acid release in adipose tissue, and impairs postprandial fatty acid uptake in the leg. These results suggest diminished fatty acid uptake and oxidation in skeletal muscle, along with enhanced fatty acid entrapment in adipose tissue, which may account for the increased adiposity in the absence of IL-6 activity. Additionally, IL-6 blockade increases the escape of meal-derived fatty acids into the bloodstream. Whether this affects fatty acid storage and lipotoxicity in other tissues warrants further investigation. This study was registered at ClinicalTrials.gov (NCT04687540).

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来源期刊
Cell Reports Medicine
Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍: Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.
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