Science Highlights | A clinical trial confirms that supplementing with NMN can enhance the body's insulin sensitivity for the first time​

Written by Hu Xiaohua, edited by Hu Xiaohua, enzyme beauty NAD+ (nicotinamide adenine dinucleotide), as a coenzyme and auxiliary substrate of some enzymes (such as sirtuins protein), participates in the regulation of many important physiological processes.

Studies in rodents have shown that insufficient NAD+ synthesis can lead to obesity and metabolic diseases related to aging [1].

In addition, during the aging process, the NAD+ level in the body was also found to be reduced [2].

Therefore, scientists are trying to improve the body's metabolic health and even reverse aging by increasing the level of NAD+ in the body, and NAD+ has become a "star molecule" in the field of metabolism.

NAD+ biosynthesis mainly relies on the Salvage pathway via NMN (nicotinamide mononucleotide), in which the production of NMN is the key rate-limiting step in NAD+ synthesis.

Pre-clinical studies have shown that feeding obese mice with NMN can increase the level of NAD+ in mice, and improve glucose tolerance and insulin sensitivity in mice [3].

The experimental success achieved in rodents allows people to see the huge application prospects of NMN.

At present, in the United States and some other countries, NMN has been developed as a health product to control blood sugar, improve energy metabolism and reverse metabolic complications caused by aging.

However, what is the role of NMN in the human body? There is still a lack of rigorous and systematic clinical trials to evaluate it.

On April 22, 2021, the Samuel Klein research team from the Human Nutrition Center of the University of Washington School of Medicine published a research article on Science titled Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women, which carried out the first clinical trial of NMN in humans.
And their research results show that NMN can enhance the insulin sensitivity of the muscle tissue of the test population.

In order to explore whether NMN can help improve the body’s metabolic health, the authors conducted a 10-week, placebo-controlled clinical trial with postmenopausal and pre-diabetic (overweight or obese) women as subjects ( Clinical Trial.
gov NCT 03151239).

They mainly investigated three physiological indicators of the subjects: 1) the level of NAD+ in muscle tissue; 2) body composition (weight, lean and fat weight) and other basic metabolic indicators (blood sugar, insulin concentration, etc.
); 3 ) Insulin sensitivity and insulin signaling in muscle tissue.

The results showed that after taking NMN (250mg/day) for 10 weeks, although subjects in the NMN group had increased levels of NAD+ in peripheral blood mononuclear cells compared with the placebo group, there was no observation in muscle tissue When the level of NAD+ increases, the level of NAD+ downstream metabolites increases, which indicates that NMN treatment may increase the turnover rate of NAD+ in the body.

In addition, the authors found that the body composition and basic metabolic indicators of the subjects in the NMN group did not change significantly before and after taking NMN.

Finally, the authors used percutaneous biopsies to examine the glucose absorption capacity of the subjects’ muscle tissues and insulin signals (phosphorylation at AKT T308 and S473 and mTOR S2448), and found that these indicators were elevated in the NMN group.
High, which means that NMN treatment can increase the insulin sensitivity of the body's muscle tissue.Next, in order to find the possible mechanism of action of NMN, the author performed RNA-seq analysis on the subject's muscle tissue.

They identified a total of 308 differentially expressed genes between the muscle tissues of the placebo group and the NMM group after receiving insulin injections.
With the help of gene cluster analysis, they found that the PDGF (Platelet-derived growth factor) signaling pathway was enriched to differences.
The most significant pathway.

Interestingly, the PDGF signaling pathway has been reported in previous studies to enhance the phosphorylation of AKT caused by insulin stimulation [4], which may provide a possible explanation for NMN to increase muscle insulin sensitivity.

Finally, to summarize.

Based on their previous research results in animal experiments [3], the research team conducted clinical verification of the physiological functions of NMN in vivo for the first time.

In general, this clinical trial has achieved good experimental expectations: NMN can increase the insulin sensitivity of the muscle tissue of obese women.

However, whether NMN is effective for other populations and the specific mechanism of NMN still need to be further explored.

Original link: https://science.
sciencemag.
org/lookup/doi/10.
1126/science.
abe9985.
DOI: 10.
1126/science.
abe9985 (2021) Platemaker: Eleven References 1.
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Yoshino, JA Baur, SI Imai, NAD+ intermediates: The biology and therapeutic potential of NMN and NR.
Cell Metab.
27, 513–528 (2018).
2.
E.
Katsyuba, M.
Romani, D.
Hofer, J.
Auwerx, NAD+ homeostasis in health and disease.
Nat Metab 2, 9–31 (2020).
3.
J.
Yoshino, KF Mills, MJ Yoon, S.
Imai, Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice Cell Metab.
14, 528–536 (2011).
4.
M.
Razmara, CH Heldin, J.
Lennartsson, Platelet-derived growth factor-induced Akt phosphorylation requires mTOR/Rictor and phospholipase C-γ1, whereas S6 phosphorylation depends on mTOR/Raptor and phospholipase D.
Cell Commun.
Signal.
11, 3 (2013).
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