Lee Sindre, Norheim Frode, Gulseth Hanne L, Langleite Torgrim M, Kolnes Kristoffer J, Tangen Daniel S, Stadheim Hans K, Gilfillan Gregor D, Holen Torgeir, Birkeland Kåre I, Jensen Jørgen, Drevon Christian A
Department of Nutrition, Institute of Basic Medical Sciences Faculty of Medicine University of Oslo, Oslo, Norway
Department of Nutrition, Institute of Basic Medical Sciences Faculty of Medicine University of Oslo, Oslo, Norway.
Physiol Rep. 2017 Mar;5(5). doi: 10.14814/phy2.13183.
The hepatokine fetuin-A can together with free fatty acids (FFAs) enhance adipose tissue (AT) inflammation and insulin resistance via toll-like receptor 4 (TLR4). Although some of the health benefits of exercise can be explained by altered release of myokines from the skeletal muscle, it is not well documented if some of the beneficial effects of exercise can be explained by altered secretion of hepatokines. The aim of this study was to examine the effect of interaction between fetuin-A and FFAs on insulin sensitivity after physical exercise. In this study, 26 sedentary men who underwent 12 weeks of combined endurance and strength exercise were included. Insulin sensitivity was measured using euglycemic-hyperinsulinemic clamp, and AT insulin resistance was indicated by the product of fasting plasma concentration of FFAs and insulin. Blood samples and biopsies from skeletal muscle and subcutaneous AT were collected. Several phenotypic markers were measured, and mRNA sequencing was performed on the biopsies. AT macrophages were analyzed based on mRNA markers. The intervention improved hepatic parameters, reduced plasma fetuin-A concentration (11%, 0.01), slightly changed FFAs concentration, and improved glucose infusion rate (GIR) (33%, 0.01) across all participants. The change in circulating fetuin-A and FFAs interacted to predict some of the change in GIR (= -42.16, =0.030), AT insulin resistance (= 0.579, =0.003), gene expression related to TLR-signaling in AT and AT macrophage mRNA (= 94.10, =0.034) after exercise. We observed no interaction effects between FFAs concentrations and leptin and adiponectin on insulin sensitivity, or any interaction effects between Fetuin-A and FFAs concentrations on skeletal muscle TLR-signaling. The relationship between FFAs levels and insulin sensitivity seemed to be specific for fetuin-A and the AT Some of the beneficial effects of exercise on insulin sensitivity may be explained by changes in circulating fetuin-A and FFAs, promoting less TLR4 signaling in AT perhaps by modulating AT macrophages.
肝脏因子胎球蛋白-A可与游离脂肪酸（FFA）一起通过Toll样受体4（TLR4）增强脂肪组织（AT）炎症和胰岛素抵抗。尽管运动对健康的一些益处可以通过骨骼肌中肌动蛋白释放的改变来解释，但运动的一些有益效果是否可以通过肝脏因子分泌的改变来解释，目前尚无充分的文献记载。本研究的目的是探讨胎球蛋白-A与FFA之间的相互作用对体育锻炼后胰岛素敏感性的影响。在本研究中，纳入了26名久坐不动的男性，他们进行了为期12周的耐力和力量联合锻炼。使用正常血糖-高胰岛素钳夹法测量胰岛素敏感性，FFA空腹血浆浓度与胰岛素的乘积表示AT胰岛素抵抗。采集骨骼肌和皮下AT的血样和活检组织。测量了几个表型标记物，并对活检组织进行了mRNA测序。基于mRNA标记物分析AT巨噬细胞。干预改善了肝脏参数，降低了血浆胎球蛋白-A浓度（约11%，P= 0.01），FFA浓度略有变化，并改善了所有参与者的葡萄糖输注率（GIR）（约33%，P=0.01）。运动后，循环中的胎球蛋白-A和FFA的变化相互作用，可预测GIR的一些变化（β=-42.16，P=0.030）、AT胰岛素抵抗（β=0.579，P=0.003）、与AT中TLR信号相关的基因表达以及AT巨噬细胞mRNA（β=94.10，P=0.034）。我们未观察到FFA浓度与瘦素和脂联素之间对胰岛素敏感性的相互作用效应，也未观察到胎球蛋白-A与FFA浓度之间对骨骼肌TLR信号的任何相互作用效应。FFA水平与胰岛素敏感性之间的关系似乎对胎球蛋白-A和AT具有特异性。运动对胰岛素敏感性的一些有益作用可能是由循环中的胎球蛋白-A和FFA的变化所解释的，这可能通过调节AT巨噬细胞减少了AT中的TLR4信号传导。
