Nestlé Institute of Health Sciences, Nestlé Research Ltd., EPFL Innovation Park, 1015 Lausanne, Switzerland.
Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36693, USA.
Nutrients. 2022 Jul 1;14(13):2752. doi: 10.3390/nu14132752.
Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly well understood. Here, we have evaluated how combinations of different NAD precursors influence intracellular NAD levels. We identified dihydronicotinic acid riboside (NARH) as a new NAD precursor in hepatic cells. Second, we demonstrate how NARH, but not any other NAD precursor, can act synergistically with nicotinamide riboside (NR) to increase NAD levels in cultured cells and in mice. Finally, we demonstrate that the large increase in NAD prompted by the combination of these two precursors is due to their chemical interaction and conversion to dihydronicotinamide riboside (NRH). Altogether, this work demonstrates for the first time that NARH can act as a NAD precursor in mammalian cells and how different NAD precursors can interact and influence each other when co-administered.
通过进化，真核生物已经发展出利用不同分子作为独立前体来生成烟酰胺腺嘌呤二核苷酸 (NAD) 的能力，NAD 是生命必需的分子。然而，这些不同的前体是否以累加或互补的方式起作用，我们还不是真正了解。在这里，我们评估了不同 NAD 前体组合如何影响细胞内 NAD 水平。我们在肝细胞中鉴定出二氢尼克酸核糖（NARH）是一种新的 NAD 前体。其次，我们证明了 NARH 但不是任何其他 NAD 前体可以与烟酰胺核糖（NR）协同作用，以增加培养细胞和小鼠中的 NAD 水平。最后，我们证明了这两种前体组合引起的 NAD 大量增加是由于它们的化学相互作用和转化为二氢烟酰胺核糖（NRH）。总之，这项工作首次表明 NARH 可以在哺乳动物细胞中作为 NAD 前体发挥作用，以及不同的 NAD 前体在共同给药时如何相互作用和影响。
