Key Points
- NMN reduced excess collagen buildup in the heart
- Mice showed improved cardiac function
- NMN reduced proteins involved in excess collagen buildup.
- NMN lowered oxidative stress in heart tissue.
Methods
Sixty 5-week-old male mice were randomized into four groups:
The diabetes model (DM) was induced via a high-fat diet and a single injection of 100 mg/kg streptozotocin (STZ), a chemical that damages the pancreas cells that make insulin.
- Control Group: 15 mice received a standard diet + citrate buffer injections every other day for 8 weeks
- DM: 15 mice received a high-fat diet + saline injections every other day for 8 weeks.
- DM+NMN: 15 mice received a high-fat diet + 500 mg/kg NMN every other day for 8 weeks
- DM+NMN+3-TYP: 15 mice received a high-fat diet + 500 mg/kg NMN every other day for 8 weeks + 50 mg/kg 3-TYP weekly for 8 weeks.
SIRT3 is a protein that helps with cellular function. Researchers used 3-TYP, a compound that blocks SIRT3, to test whether NMN was working through it.
NMN Improved Heart Structure and Function
Diabetic mice showed changes in heart structure and function, including an increased heart size and different amounts of blood in one side, along with lower measures of cardiac pumping function.
“Assessment revealed a significant increase in the heart-to-tibia ratio within the DM group.”
When SIRT3 was blocked with 3-TYP, these effects were reduced, suggesting that SIRT3 may contribute to NMN’s observed effects.
“The effects observed with NMN were reduced when SIRT3 was inhibited with 3-TYP, suggesting that SIRT3 may contribute to NMN-associated changes in cardiac function”.
This graph shows how the DM+NMN group bar (dark cyan) moved toward the control group bar (light orange), indicating a significant improvement in the DM+NMN heart size; whereas the DM group (mint) and the DM+NMN+3-TYP (periwinkle) showed an increase in heart size relative to the control group.
“While this metric showed significant improvement in the DM+NMN group, the beneficial effect of NMN was substantially inhibited by 3-TYP.”
NMN Reduced Collagen Buildup in the Heart
Researchers found more collagen and changes to the structure of heart tissue in the diabetic mice. Those changes were smaller in the mice that received NMN.
Myocardial interstitial fibrosis
| Group | Fibrosis area |
|---|---|
| Control | 1.26% |
| DM | 5.75% |
| DM + NMN | 1.94% |
| DM + NMN + 3-TYP | 4.92% |
“Escalation of collagen deposition within the heart tissue of the DM mice group, an effect that was significantly attenuated by NMN mediation for the other models”.
In the diabetic mice, NMN lowered the amount of extra collagen in the heart, bringing it close to what was seen in the healthy control mice.
Blocking SIRT3 reduced this effect. Relative to diabetic mice, NMN lowered the measured fibrosis area by approximately 66%.
NMN Lowered Oxidative Stress in the Heart
Diabetic mice’s hearts showed much higher levels of reactive oxygen species (ROS) than the healthy control mice.
“Overproduction of ROS triggers oxidative stress, a key driver of insulin resistance”.
NMN treatment lowered DHE fluorescence signal, consistent with lower local ROS accumulation, whereas blocking SIRT3 with 3-TYP reversed much of this effect.
NMN has been linked to improved oxidative stress and mitochondrial health in heart tissue.
Conclusion
This study provides preclinical insights into the effects of NMN on heart structure and function in a diabetic mouse model.
“NMN was associated with improvements in several measures of cardiac structure and function, including heart-to-tibia ratio, left ventricular volumes, ejection fraction, and fractional shortening”.
NMN also reduced collagen buildup in the heart and lowered oxidative stress.
“These findings suggest that the SIRT3 pathway may be involved in the response observed with NMN.”
These data provide preclinical evidence for continued research into NMN and its potential role in healthy aging and physiological function.
