Nmrk1, also known as nicotinamide riboside kinase 1, is an essential enzyme in the utilization of nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+). NAD+ is a co-enzyme in redox reactions and a substrate for various enzyme families. Nmrk1 is thus crucial for maintaining NAD+ biosynthesis. It is involved in multiple biological processes related to energy metabolism, and its dysregulation may be associated with metabolic and age-related diseases [1,2,3,4].

In whole-body and pancreatic β-cell-specific Nmrk1 knockout (KO) mice, high-fat feeding or aging led to glucose intolerance and compromised β-cell response to a glucose challenge, suggesting that Nmrk1 is important for maintaining glucose tolerance and pancreatic β-cell function in such pathophysiological conditions [2]. In whole-body and liver-specific Nmrk1 KO mice, high-fat feeding resulted in decreased gluconeogenic potential, impaired mitochondrial function, glucose intolerance, insulin resistance, and hepatosteatosis, indicating that endogenous Nmrk1-mediated NR metabolism is critical to sustain hepatic NAD+ levels and prevent diet-induced metabolic damage [3].

In conclusion, Nmrk1 is vital for maintaining NAD+ levels, which is essential for energy metabolism-related processes. The study of Nmrk1 KO mouse models has revealed its significance in pancreatic β-cell function and glucose homeostasis, as well as in preventing diet-induced liver metabolic damage, providing insights into its role in metabolic and age-related diseases.

References:

1. Fan, Rui, Cui, Jing, Ren, Feng, Qian, Xinlai, Xiong, Xiwen. . Overexpression of NRK1 ameliorates diet- and age-induced hepatic steatosis and insulin resistance. In Biochemical and biophysical research communications, 500, 476-483. doi:10.1016/j.bbrc.2018.04.107. https://pubmed.ncbi.nlm.nih.gov/29678570/

2. Cercillieux, Angelique, Ratajczak, Joanna, Joffraud, Magali, Sambeat, Audrey, Canto, Carles. 2022. Nicotinamide riboside kinase 1 protects against diet and age-induced pancreatic β-cell failure. In Molecular metabolism, 66, 101605. doi:10.1016/j.molmet.2022.101605. https://pubmed.ncbi.nlm.nih.gov/36165811/

3. Sambeat, Audrey, Ratajczak, Joanna, Joffraud, Magali, Moco, Sofia, Canto, Carles. 2019. Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage. In Nature communications, 10, 4291. doi:10.1038/s41467-019-12262-x. https://pubmed.ncbi.nlm.nih.gov/31541116/

4. Chi, Yuling, Sauve, Anthony A. . Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. In Current opinion in clinical nutrition and metabolic care, 16, 657-61. doi:10.1097/MCO.0b013e32836510c0. https://pubmed.ncbi.nlm.nih.gov/24071780/