Vamvini Maria, Nigro Pasquale, Caputo Tiziana, Stanford Kristin I, Hirshman Michael F, Middelbeek Roeland J W, Goodyear Laurie J
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
bioRxiv. 2023 Oct 18:2023.10.16.562635. doi: 10.1101/2023.10.16.562635.
Exercise training and cold exposure both improve systemic metabolism, but the mechanisms are not well-established. We tested the hypothesis that adaptations to inguinal white adipose tissue (iWAT) are critical for these beneficial effects by determining the impact of exercise-trained and cold-exposed iWAT on systemic glucose metabolism and the iWAT proteome and secretome. Transplanting trained iWAT into sedentary mice improved glucose tolerance, while cold-exposed iWAT transplantation showed no such benefit. Compared to training, cold led to more pronounced alterations in the iWAT proteome and secretome, downregulating >2,000 proteins but also boosting iWAT's thermogenic capacity. In contrast, only training increased extracellular space and vesicle transport proteins, and only training upregulated proteins that correlate with favorable fasting glucose, suggesting fundamental changes in trained iWAT that mediate tissue-to-tissue communication. This study defines the unique exercise training- and cold exposure-induced iWAT proteomes, revealing distinct mechanisms for the beneficial effects of these interventions on metabolic health.
运动训练和冷暴露均可改善全身代谢，但其机制尚未完全明确。我们通过确定运动训练和冷暴露的腹股沟白色脂肪组织（iWAT）对全身葡萄糖代谢以及iWAT蛋白质组和分泌组的影响，来检验以下假设：iWAT的适应性变化对于这些有益作用至关重要。将经过训练的iWAT移植到久坐不动的小鼠体内可改善葡萄糖耐量，而冷暴露的iWAT移植则未显示出此类益处。与运动训练相比，冷暴露导致iWAT蛋白质组和分泌组发生更显著的变化，下调了2000多种蛋白质，但同时也增强了iWAT的产热能力。相反，只有运动训练增加了细胞外空间和囊泡运输蛋白，只有运动训练上调了与空腹血糖良好相关的蛋白质，这表明经过训练的iWAT发生了根本性变化，从而介导组织间通讯。本研究定义了运动训练和冷暴露诱导产生的独特的iWAT蛋白质组，揭示了这些干预措施对代谢健康产生有益影响的不同机制。
