Almost 40% of adults worldwide are classified as overweight or obese. Exercise is a beneficial intervention in obesity, partly due to increases in mitochondrial activity, and subsequent increases in nicotinamide adenine dinucleotide (NAD⁺), an important metabolic cofactor. Recent studies have shown that increasing NAD⁺ levels through pharmacological supplementation with precursors such as nicotinamide mononucleotide (NMN) improved metabolic health in high fat diet (HFD) fed mice. However, the effects of combined exercise and NMN supplementation are unknown. Thus here we examined the combined effects of NMN and treadmill exercise in female mice with established obesity after 10 weeks of diet. Five-week old female C57BL/6J mice were exposed to control diet (n=16) or HFD. Sedentary mice fed HFD were either untreated (HFD; n=16), received NMN in drinking water (400mg/kg; HNMN; n=16), were exposed to treadmill exercise 6 days/week (HEx; n=16) or exercise combined with NMN (HNEx; n=16). Whilst some metabolic benefits of NMN have been described, at this dose, NMN administration impaired several aspects of exercise-induced benefits in obese mice, including glucose tolerance, glucose stimulated insulin secretion from islets and reduced hepatic triglyceride accumulation. HNEx mice also exhibited increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN co-treatment. Our data show that NMN treatment impedes the beneficial metabolic effects of exercise in a mouse model of diet-induced obesity in association with disturbances in redox metabolism.

中文翻译：

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同时烟酰胺单核苷酸降低了运动诱导的饮食诱导肥胖模型中葡萄糖处理的益处

全球近 40% 的成年人被归类为超重或肥胖。运动是对肥胖的有益干预，部分原因是线粒体活性增加，随后烟酰胺腺嘌呤二核苷酸 (NAD ⁺ )（一种重要的代谢辅因子）增加。最近的研究表明，增加 NAD ⁺通过药理学补充烟酰胺单核苷酸 (NMN) 等前体，改善了高脂肪饮食 (HFD) 喂养小鼠的代谢健康。然而，联合运动和补充 NMN 的效果尚不清楚。因此，在这里，我们检查了 NMN 和跑步机运动对 10 周饮食后已确定肥胖的雌性小鼠的综合影响。五周大的雌性 C57BL/6J 小鼠暴露于对照饮食 (n=16) 或 HFD。喂食 HFD 的久坐小鼠未经治疗（HFD；n=16），在饮用水中接受 NMN（400mg/kg；HNMN；n=16），每周 6 天进行跑步机运动（HEx；n=16）或运动结合 NMN（HNEx；n=16）。虽然已经描述了 NMN 的一些代谢益处，但在此剂量下，NMN 给药会损害肥胖小鼠运动诱导益处的几个方面，包括葡萄糖耐量、葡萄糖刺激胰岛的胰岛素分泌和减少肝脏甘油三酯的积累。HNEx 小鼠的胰岛和肌肉中的抗氧化基因表达也增加，促氧化基因表达降低，这表明氧化还原状态的改变与 NMN 联合治疗时运动诱导的健康益处的丧失有关。我们的数据表明，NMN 治疗阻碍了与氧化还原代谢紊乱相关的饮食诱导肥胖小鼠模型中运动的有益代谢作用。表明改变的氧化还原状态与运动诱发的 NMN 联合治疗的健康益处的丧失有关。我们的数据表明，NMN 治疗阻碍了与氧化还原代谢紊乱相关的饮食诱导肥胖小鼠模型中运动的有益代谢作用。表明改变的氧化还原状态与 NMN 联合治疗时运动引起的健康益处的丧失有关。我们的数据表明，NMN 治疗阻碍了与氧化还原代谢紊乱相关的饮食诱导肥胖小鼠模型中运动的有益代谢作用。