Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells.
Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells.
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DOI：
10.1016/j.redox.2017.04.009
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发表时间：
2017-08
期刊：
影响因子：
11.4
通讯作者：
Newsholme P
中科院分区：
文献类型：
--
作者：
Calton EK;Keane KN;Raizel R;Rowlands J;Soares MJ;Newsholme P
维生素D状态[25(OH)D]最近被报道与外周血单核细胞（PBMCs）细胞生物能量谱的改变有关。目前还没有研究追踪25(OH)D的季节性变化及其对全身能量代谢、细胞生物能量谱、炎症标志物和临床化学的可能影响。用间接量热法测定全身能量代谢和底物利用率。从同一受试者的全血中分离PBMCs，计数并新鲜播种。采用Seahorse XFe96通量分析仪进行生物能量分析（线粒体压力测试和糖酵解压力测试）。采用Architect免疫分析法评估25(OH)D。25(OH)D的中位数（IQR）在冬季和夏季增加了14.40 (20.13)nmol/L (p<0.001)，并伴有胰岛素敏感性指标、McAuley指数（p=0.019）和胰岛素敏感性定量检查指数（p=0.028）的显著改善。与冬季相比，PBMC线粒体参数基础呼吸、非线粒体呼吸、ATP生成、质子泄漏和最大呼吸在夏季下降。同样，PBMC糖酵解参数糖酵解活性、葡萄糖反应和糖酵解能力在夏季都比冬季降低。绝对静息代谢率（RMR）也有下降趋势（p=0.066）。全身炎症标志物MCP-1、IL-6、IL-8、IL-10和IL-12p70在夏季较冬季显著降低。与冬季25(OH)D浓度为50 - 75 nmol/L或50 - 75 nmol/L的参与者相比，进入冬季时25(OH)D浓度较低（<50 nmol/L）的参与者在夏季的生物能量参数变化最大。25(OH)D的绝对变化与生物能量学的改变无关。25(OH)D的季节性改善与全身炎症、PBMC生物能量谱和全身能量代谢的减少有关。这些PBMC生物能量学的变化在冬季25(OH)D不足的人群中最为明显。这些数据值得通过因果研究设计来证实。夏季与冬季相比，炎症和临床生化指标有所改善。25(OH)D的季节性改善调节了pbmc的生物能量分布。维持25(OH)D bb0 - 50 nmol/L可能对生物能量功能很重要。
Vitamin D status [25(OH)D] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs). No study has tracked the seasonal variation of 25(OH)D and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry. Whole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test) was performed using the Seahorse XFe96 flux analyser. 25(OH)D was assessed using the Architect immunoassay method. 25(OH)D increased by a median (IQR) of 14.40 (20.13) nmol/L (p<0.001) from winter to summer and was accompanied by significant improvements in indices of insulin sensitivity, McAuley's index (p=0.019) and quantitative insulin sensitivity check index (p=0.028). PBMC mitochondrial parameters basal respiration, non-mitochondrial respiration, ATP production, proton leak, and maximal respiration decreased in summer compared to winter. Similarly, PBMC glycolytic parameters glycolytic activity, glucose response, and glycolytic capacity were all reduced in summer compared to winter. There was also a trend for absolute resting metabolic rate (RMR) to decrease (p=0.066). Markers of systemic inflammation MCP-1, IL-6, IL-8, IL-10, and IL-12p70 decreased significantly in summer compared to winter. Participants who entered winter with a low 25(OH)D (<50 nmol/L), had the greatest alteration in bioenergetic parameters in summer, relative to those with winter 25(OH)D concentrations of 50–75 nmol/L or >75 nmol/L. The absolute change in 25(OH)D was not associated with altered bioenergetics. Seasonal improvements in 25(OH)D was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OH)D in winter. The data warrants confirmation through cause and effect study designs. Inflammation and clinical biochemistry improved in summer versus winter. Seasonal improvements in 25(OH)D modulated the bioenergetic profile of PBMCs. Maintaining 25(OH)D >50 nmol/L may be important for bioenergetic function.