Journal
FRONTIERS IN CARDIOVASCULAR MEDICINE
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2021.721814
Keywords
1-methylnicotinamide; free fatty acids; inflammation; apoptosis; fibrosis; Nrf2; NFkB
Categories
Funding
- National Natural Science Foundation of China
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High levels of free fatty acids are closely associated with obesity and cardiovascular diseases, with NAD metabolism emerging as a potential target. The study revealed that 1-MNA may prevent heart injury induced by high fatty diets and PA by regulating Nrf2 and NF-κB pathways.
High levels of free fatty acids (FFA) are closely associated with obesity and the development of cardiovascular diseases. Recently, nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a potential target for several modern diseases including diabetes. Herein, we explored the underlying mechanisms of NAD metabolism associated with the risk of cardiovascular disease. Our study found that nicotinamide N-methyltransferase (NNMT) mRNA levels were significantly increased in the hearts of FFA-bound-albumin-overloaded mice and in H9C2 cells treated with palmitic acid (PA). We studied the mechanisms underlining the anti-inflammatory and anti-oxidant activities of 1-methylnicotinamide (1-MNA), a metabolite of NNMT. We found a significantly higher level of reactive oxygen species, inflammation, apoptosis, and cell hypertrophy in PA-treated H9C2 cells and this effect was inhibited by 1-MNA treatment. in vivo, 1-MNA improved inflammation, apoptosis, and fibrosis damage in mice and this inhibition was associated with inhibited NF-kappa B activity. In conclusion, our study revealed that 1-MNA may prevent high fatty diet and PA-induced heart injury by regulating Nrf2 and NF-kappa B pathways.
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