消瘦综合症是一种令人衰弱的症状，是癌症患者常见的共病。它主要表现为与能量和线粒体代谢异常有关，从而促进组织消耗。我们最近发现，尼古丁酸腺嘌呤二核苷酸（NAD +）的损失与癌症宿主肌肉线粒体功能障碍有关。在本研究中，我们证实NAD +耗竭和Nrk2下调（一种NAD +生物合成酶）是不同小鼠模型中严重消瘦的共同特点。在消瘦小鼠中测试NAD +补充治疗，结果表明NAD +前体维生素B3烟酸可以有效纠正组织NAD +水平，改善线粒体代谢并缓解癌症和化疗引起的消瘦症状。在临床环境中，我们发现肌肉NRK2在癌症患者中下调。NRK2的低表达与代谢异常相关，强调NAD +在人类癌症消瘦症理疗中的重要性。总体而言，我们的研究表明NAD +代谢是治疗癌症消瘦症患者的一个治疗靶点。©2023.作者（们）。

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients.© 2023. The Author(s).