Nicotinamide riboside|1341-23-7|安捷凯

Background

Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, is converted to bioavailable NAD+, via nicotinamide riboside kinase (NRK) and NMNAT, or by the action of nucleoside phosphorylase and NAM salvage^[1-2].

In in vitro experiments ,nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway ^[3]. Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans^[4].

Nicotinamide Riboside was able to enhance the skeletal muscle NAD+ metabolome, inducing gene expression signatures implicated in downregulation of energy metabolism pathways, but did not affect muscle mitochondrial bioenergetics or metabolism^[5]. Nicotinamide Riboside enhances deacetylase activity in vivo, deacetylates PGC-1α in muscle, liver, and BAT, and it induces deacetylase activity in tissues where NAD+ accumulates^[6].

参考文献:
[1] Bieganowski P., Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell.2004;117:495–502.
[2] Nikiforov A., Dolle C., Niere M. Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation. J. Biol. Chem. 2011;286:21767–21778.
[3] Wang S, Wan T, et al. Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway. Redox Biol. 2018 Jul;17:89-98.
[4] Nascimento EBM, Moonen MPB, et al. Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans. J Clin Endocrinol Metab. 2021 Apr 23;106(5):1437-1447.
[5] Elhassan YS, Kluckova K, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019 Aug 13;28(7):1717-1728.e6.
[6] Cantó C, Houtkooper RH,et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47.

烟酰胺核苷是维生素 B3 和 NAD+ 前体的一种形式，通过烟酰胺核苷激酶 (NRK) 和 NMNAT，或通过核苷磷酸化酶和 NAM 补救作用，转化为生物可利用的 NAD+^[1-2].

在体外实验中，烟酰胺核苷通过激活 SirT1/PGC-1α/线粒体生物合成途径减轻酒精引起的肝损伤^[3]。烟酰胺核苷增强人体体外 β-肾上腺素能棕色脂肪组织活性^[4]。

烟酰胺核苷能够增强骨骼肌 NAD+ 代谢组，诱导与能量代谢途径下调有关的基因表达特征，但不影响肌肉线粒体生物能量学或代谢^[5]。烟酰胺核苷在体内增强脱乙酰酶活性，使肌肉、肝脏和BAT中的PGC-1α脱乙酰化，并在NAD+积累的组织中诱导脱乙酰酶活性^[6]。

Protocol

Cell experiment [1]:

Cell lines

Murine RAW 264.7 macrophages

Preparation Method

The prepared mouse bone marrow-derived macrophages were cultured and stored at 37°C in 5% CO2. Murine RAW 264.7 macrophages were treated with EtOH (80?mM), MeCHO (200?μM), and nicotinamide riboside (1?mM), respectively, and ROS accumulation was determined.

Reaction Conditions

1?mM ,72?h

Applications

Ethanol and its metabolite, acetaldehyde, significantly increased cellular ROS levels, but Nicotinamide riboside completely abolished the increase to a basal level in RAW 264.7 macrophages.

Animal experiment [2]:

Animal models

Eight-week-old male C57BL/6?J mice

Preparation Method

The reared mice were randomly divided into 3 groups: control group (CTRL), ethanol group (EtOH) and nicotinamide riboside supplementation group (EtOH+ Nicotinamide riboside ). Mice in the ethanol and nicotinamide riboside supplemented groups were fed a Lieber-DeCarli ethanol liquid diet, while control mice were paired as previously described.

Dosage form

400?mg/kg, oral gavage once daily for 10 consecutive days

Applications

Mice were fed in pairs and there was no difference in body weight between the three groups. Fat accumulation was observed in the ethanol group, while only a few tiny lipid droplets were observed in the nicotinamide riboside group. Nicotinamide riboside significantly decreased serum ALT and AST and liver triglyceride levels, and slightly decreased liver weight ratio.

参考文献:

[1]. Wang S, Wan T,et al. Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway. Redox Biol. 2018 Jul;17:89-98.

[2]. Kang H, Park YK, Lee JY. Nicotinamide riboside, an NAD+ precursor, attenuates inflammation and oxidative stress by activating sirtuin 1 in alcohol-stimulated macrophages. Lab Invest. 2021 Sep;101(9):1225-1237.

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Nicotinamide riboside

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Background

Protocol

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