Ward Kiera, Mulder Edwin, Frings-Meuthen Petra, O'Gorman Donal J, Cooper Diane
Faculty of Science and Health, Technological University of the Shannon, Athlone Campus, Athlone, Ireland.
Department of Muscle and Bone Metabolism, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.
Front Physiol. 2024 Sep 10;15:1435448. doi: 10.3389/fphys.2024.1435448. eCollection 2024.
Alterations in the circulating concentrations and target-tissue action of organokines underpin the development of insulin resistance in microgravity and gravity deprivation. The purpose of this study was to examine changes in circulating adropin, irisin, retinol binding protein-4 (RBP4), and the metabolic response of healthy young males following 60 days of 6° head-down-tilt (HDT) bed rest, with and without reactive jump training (RJT), to explore links with whole-body and tissue-specific insulin sensitivity. To our knowledge, this is the first time that adropin, irisin, and RBP4 have been studied in HDT bed rest.
A total of 23 male subjects (29 ± 6 years, 181 ± 6 cm, 77 ± 7 kg) were exposed to 60 days of 6° HDT bed rest and randomized to a control (CTRL, n = 11) or a RJT (JUMP, n = 12) group (48 sessions with ≤4 min total training time per session). Circulating adropin, irisin, and RBP4 were quantified in fasting serum before and after HDT bed rest. A subanalysis was performed to investigate individual metabolic responses post-HDT bed rest based on subjects that showed an increase or decrease in whole-body insulin sensitivity (Matsuda index).
There were significant main effects of time, but not group, for decreases in adropin, irisin, Matsuda index, and liver insulin sensitivity following HDT bed rest ( < 0.05), whereas RBP4 did not change. The subanalysis identified that in a subgroup with decreased whole-body insulin sensitivity (n = 17), RBP4 increased significantly, whereas adropin, irisin, and liver insulin sensitivity were all decreased significantly following HDT bed rest. Conversely, in a subgroup with increased whole-body insulin sensitivity (n = 6), liver insulin sensitivity increased significantly after HDT bed rest, whereas adropin, irisin, and RBP4 did not change.
Investigating individual metabolic responses has provided insights into changes in circulating adropin, irisin, RBP4, in relation to insulin sensitivity following HDT bed rest. We conclude that adropin, irisin, and RBP4 are candidate biomarkers for providing insights into whole-body and tissue-specific insulin sensitivity to track changes in physiological responsiveness to a gravity deprivation intervention in a lean male cohort.
器官因子循环浓度和靶组织作用的改变是微重力和失重状态下胰岛素抵抗发展的基础。本研究旨在检测健康年轻男性在60天6°头低位卧床休息（HDT）期间，无论有无反应性跳跃训练（RJT），循环中内脂素、鸢尾素、视黄醇结合蛋白4（RBP4）的变化以及代谢反应，以探索与全身和组织特异性胰岛素敏感性的联系。据我们所知，这是首次在HDT卧床休息中对内脂素、鸢尾素和RBP4进行研究。
总共23名男性受试者（29±6岁，181±6厘米，77±7千克）接受60天6°HDT卧床休息，并随机分为对照组（CTRL，n = 11）或RJT组（JUMP，n = 12）（共48节训练课，每节训练课总时长≤4分钟）。在HDT卧床休息前后，对空腹血清中的循环内脂素、鸢尾素和RBP4进行定量分析。根据全身胰岛素敏感性（松田指数）升高或降低的受试者，进行亚组分析以研究HDT卧床休息后的个体代谢反应。
HDT卧床休息后，内脂素、鸢尾素、松田指数和肝脏胰岛素敏感性降低存在显著的时间主效应，但无组间主效应（P<0.05），而RBP4没有变化。亚组分析发现，在全身胰岛素敏感性降低的亚组（n = 17）中，HDT卧床休息后RBP4显著升高，而内脂素、鸢尾素和肝脏胰岛素敏感性均显著降低。相反，在全身胰岛素敏感性升高的亚组（n = 6）中，HDT卧床休息后肝脏胰岛素敏感性显著升高，而内脂素、鸢尾素和RBP4没有变化。
通过研究个体代谢反应，我们深入了解了HDT卧床休息后循环内脂素、鸢尾素、RBP4与胰岛素敏感性的变化。我们得出结论，内脂素、鸢尾素和RBP4是候选生物标志物，有助于了解全身和组织特异性胰岛素敏感性，以追踪瘦男性队列中对失重干预的生理反应变化。
