Voluntary running and IV nicotinamide riboside synergise to boost mouse skeletal muscle NAD+ without impacting OXPHOS capacity or insulin sensitivity

In clinical trials, oral supplementation with nicotinamide riboside (NR) fails to increase muscle mitochondrial respiratory capacity and insulin sensitivity, but also does not increase muscle NAD+ levels. This study tests the feasibility of chronically elevating skeletal muscle NAD+ in mice and investigates the putative effects on mitochondrial respiratory capacity, insulin sensitivity, and gene expression. Accordingly, to improve bioavailability to skeletal muscle, we developed an experimental model for administering NR repeatedly through a jugular vein catheter. Mice on a Western diet were treated with various combinations of NR, pterostilbene (PT), and voluntary wheel running, but metabolic effects of NR and PT treatment were modest. We conclude that chronic elevation of skeletal muscle NAD+ by intravenous injection of NR is possible but does not affect muscle respiratory capacity or insulin sensitivity in either sedentary or physically active mice. Our data have implications for NAD+ precursor supplementation regimes. Overall design: 2^3 full-factorial setup with the three factors nicotinamide riboside (NR), pterostilbene (PT) and voluntary wheel running

在临床试验中，口服烟酰胺核糖（nicotinamide riboside, NR）补充剂未能提升肌肉线粒体呼吸能力与胰岛素敏感性，亦未升高肌肉NAD+水平。本研究旨在检验在小鼠体内长期升高骨骼肌NAD+水平的可行性，并探究其对线粒体呼吸能力、胰岛素敏感性及基因表达的潜在效应。为提升骨骼肌对NR的生物利用度，我们开发了一种通过颈静脉导管反复给予NR的实验模型。本研究对西式饮食喂养的小鼠采用NR、紫檀芪（pterostilbene, PT）与自愿转轮运动的不同组合进行干预，但NR与PT处理的代谢效应较为微弱。我们得出结论：通过静脉注射NR以长期升高骨骼肌NAD+水平是可行的，但无论在久坐还是运动活跃的小鼠中，均未对肌肉呼吸能力或胰岛素敏感性产生影响。本研究数据可为NAD+前体补充方案提供参考。实验设计：采用2^3全因子实验设置，包含三个干预因素：烟酰胺核糖（NR）、紫檀芪（PT）与自愿转轮运动。