Background
β-nicotinamide mononucleotide is a product of the nicotinamide phosphoribosyltransferase (NAMPT) reaction and a key NAD+ intermediate. The pharmacological activities of β-nicotinamide mononucleotide include its role in cellular biochemical functions, cardioprotection, diabetes, Alzheimer's disease, and complications associated with obesity[1].
Intracellular NAD + levels were significantly reduced by knocking down or knocking down Nampt or treated with the Nampt inhibitor FK866, whereas NAD + levels were significantly increased by supplementation with NAD + precursors NAM or β-Nicotinamide mononucleotide [3].Treatment of β-nicotinamide mononucleotide, a precursor of NAD+, to HEK293 cells activated and improved the rate of mtDNA replication by increasing nucleotides in mitochondria and decreasing their degradation products: nucleosides. β-Nicotinamide mononucleotide metabolism plays a role in supporting mtDNA replication by maintaining the nucleotide pool balance in the mitochondria[7].
After β-Nicotinamide mononucleotide administration, there was no difference in blood glucose levels in GTTs between Nampt+/- and control female mice. In addition, β-Nicotinamide mononucleotide-treated Nampt+/- and control mice also had similar plasma insulin levels at each time point. β-Nicotinamide mononucleotide administration corrects the defect in GSIS observed in Nampt+/- mice[2]. β-nicotinamide mononucleotide ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. β-nicotinamide mononucleotide also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation[4].In a mouse model induced by doxorubicin administered in divided low doses as in the clinics, supplementing mice with a precursor of NAD+ prevented the mtDNA depletion and cardiac dysfunction[5].When investigated whether β-Nicotinamide mononucleotide is superior to nicotinamide (Nam) as a precursor of NAD+ in whole animal experiments. β-Nicotinamide mononucleotide is retained in the body for longer than Nam[6].
β-烟酰胺单核苷酸是烟酰胺磷酸核糖转移酶（NAMPT）反应的产物，也是关键的NAD+中间体。β-烟酰胺单核苷酸的药理活性包括其在细胞生化功能、心脏保护、糖尿病、阿尔茨海默氏症以及与肥胖相关并发症方面的作用[1]。
通过敲除或抑制Nampt，或使用Nampt抑制剂FK866处理，细胞内NAD+水平显著降低；而通过补充NAD+前体物质NAM或β-烟酰胺单核苷酸，则可以显著增加NAD+水平。将β-烟酰胺单核苷酸作为NAD+的前体物质添加到HEK293细胞中，可以通过增加线粒体中的核苷酸并减少其降解产物（即核苷）来激活和改善mtDNA复制速率。 β-烟酰胺单核苷酸代谢在支持mtDNA复制方面发挥作用，通过保持线粒体中的核苷酸池平衡来实现这一点。
在给β-烟酰胺单核苷酸注射后，Nampt+/-和对照组雌性小鼠的葡萄糖耐量试验中血糖水平没有差异。此外，接受β-烟酰胺单核苷酸治疗的Nampt+/-和对照组小鼠在每个时间点上也具有相似的血浆胰岛素水平。 β- 烟酰胺单核苷酸治疗纠正了观察到的Nampt+/-小 鼠中GSIS缺陷[2]。 β- 烟 酰 胺 单 核 苷 酸 通过恢复HFD诱导T2D小 鼠中NAD + 水平来改善葡萄 糖不耐受性。 β - 烟 酰 胺 单 核 苷 酸 还通过SIRT1激活部分增强肝脏胰岛素敏感性并恢复与氧化应激、炎性反应和昼夜节律相关基因表达[4]。 在以分割低剂量多柔比星诱导的小鼠模型中，用NAD + 前体物质补充可以防止mtDNA消耗和心脏功能障碍[5]。当研究β- 烟 酰 胺 单 核 苷 酸 是否优于烟酰胺（Nam）作为NAD + 前体物质的整体动物实验时，发现β- 烟 酰 胺 单 核 苷 酸在体内的保留时间比Nam长[6]。
参考文献:
[1]: Poddar SK, Sifat AE, et,al. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. 2019 Jan 21;9(1):34. doi: 10.3390/biom9010034. PMID: 30669679; PMCID: PMC6359187.
[2]: Revollo JR, K?rner A, et,al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007 Nov;6(5):363-75. doi: 10.1016/j.cmet.2007.09.003. PMID: 17983582; PMCID: PMC2098698.
[3]: Lv H, Lv G, et,al. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metab. 2021 Jan 5;33(1):110-127.e5. doi: 10.1016/j.cmet.2020.10.021. Epub 2020 Nov 9. PMID: 33171124.
[4]:Yoshino J, Mills KF, et,al. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011 Oct 5;14(4):528-36. doi: 10.1016/j.cmet.2011.08.014. PMID: 21982712; PMCID: PMC3204926.
[5]: Li J, Wang PY, et,al. p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities. Proc Natl Acad Sci U S A. 2019 Sep 24;116(39):19626-19634. doi: 10.1073/pnas.1904979116. Epub 2019 Sep 5. PMID: 31488712; PMCID: PMC6765288.
[6]: Kawamura T, Mori N, et,al. β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats. J Nutr Sci Vitaminol (Tokyo). 2016;62(4):272-276. doi: 10.3177/jnsv.62.272. PMID: 27725413.
[7]:Cros C, Margier M, et,al. Nicotinamide Mononucleotide Administration Triggers Macrophages Reprogramming and Alleviates Inflammation During Sepsis Induced by Experimental Peritonitis. Front Mol Biosci. 2022 Jun 27;9:895028. doi: 10.3389/fmolb.2022.895028. PMID: 35832733; PMCID: PMC9271973.
Protocol
| Cell experiment [1]: |
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Cell lines
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Hepa1-6 cells
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Preparation Method
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β-Nicotinamide mononucleotide was added to the cell medium
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Reaction Conditions
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0.5-1 mMβ-Nicotinamide mononucleotide
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Applications
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Intracellular NAD + levels were significantly reduced by knocking down or knocking down Nampt or treated with the Nampt inhibitor FK866, whereas NAD + levels were significantly increased by supplementation with NAD + precursors NAM or β-Nicotinamide mononucleotide.
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| Animal experiment [2]: |
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Animal models
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Nampt+/- female mice
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Preparation Method
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For GTTs, mice were injected with PBS or β-Nicotinamide mononucleotide (500 mg/kg body weight) and fasted for 14 hrs; dextrose (3 g/kg body weight) was then injected intraperitoneally.
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Dosage form
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500 mg/kg β-Nicotinamide mononucleotide for 0、15、30、60,120min
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Applications
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After β-Nicotinamide mononucleotide administration, there was no difference in blood glucose levels in GTTs between Nampt+/- and control female mice. In addition, β-Nicotinamide mononucleotide-treated Nampt+/- and control mice also had similar plasma insulin levels at each time point. β-Nicotinamide mononucleotide administration corrects the defect in GSIS observed in Nampt+/- mice.
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参考文献:
[1]: Lv H, Lv G, et,al. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metab. 2021 Jan 5;33(1):110-127.e5. doi: 10.1016/j.cmet.2020.10.021. Epub 2020 Nov 9. PMID: 33171124.
[2]: Revollo JR, K?rner A, et,al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007 Nov;6(5):363-75. doi: 10.1016/j.cmet.2007.09.003. PMID: 17983582; PMCID: PMC2098698.
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