Department of Developmental Biology, Washington University School of Medicine,, St. Louis, MO 63110, USA.
Center for Human Nutrition, Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Nat Metab. 2019 Jan;1(1):47-57. doi: 10.1038/s42255-018-0009-4. Epub 2019 Jan 7.
Nicotinamide mononucleotide (NMN) is a biosynthetic precursor of NAD known to promote cellular NAD production and counteract age-associated pathologies associated with a decline in tissue NAD levels. How NMN is taken up into cells has not been entirely clear. Here we show that the gene encodes a specific NMN transporter. We find that is highly expressed and regulated by NAD in the murine small intestine. knockdown abrogates the uptake of NMN and . We further show that Slc12a8 specifically transports NMN, but not nicotinamide riboside, and that NMN transport depends on the presence of sodium ion. deficiency significantly decreases NAD levels in the jejunum and ileum, which is associated with reduced NMN uptake as traced by doubly labeled isotopic NMN. Finally, we observe that expression is upregulated in the aged murine ileum, which contributes to the maintenance of ileal NAD levels. Our work identifies the first NMN transporter and demonstrates that Slc12a8 has a critical role in regulating intestinal NAD metabolism.
烟酰胺单核苷酸 (NMN) 是 NAD 的生物合成前体，已知可促进细胞 NAD 产生并对抗与组织 NAD 水平下降相关的与年龄相关的病理学。NMN 如何被细胞吸收尚不完全清楚。在这里，我们表明 基因编码一种特定的 NMN 转运蛋白。我们发现 在小鼠小肠中高度表达并受 NAD 调节。 敲低会破坏 NMN 和 的摄取。我们进一步表明 Slc12a8 特异性转运 NMN，但不转运烟酰胺核苷，并且 NMN 转运依赖于钠离子的存在。 缺乏会显着降低空肠和回肠中的 NAD 水平，这与通过双重标记同位素 NMN 追踪到的 NMN 摄取减少有关。最后，我们观察到 在衰老的小鼠回肠中表达上调，这有助于维持回肠 NAD 水平。我们的工作确定了第一个 NMN 转运蛋白，并表明 Slc12a8 在调节肠道 NAD 代谢中具有关键作用。
