Title
Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease
Background
Persistent alcohol consumption globally contributes significantly to liver disease. Various biochemical processes, including oxidative stress, inflammation, and disruptions in NAD+/NADH, are associated with the initiation and progression of alcoholic liver disease (ALD). Notably, the reduction in hepatic NAD+ levels due to ethanol is believed to contribute to ethanol-induced conditions like steatosis, oxidative stress, steatohepatitis, insulin resistance, and gluconeogenesis inhibition. To explore changes in early-stage ALD pathogenesis, we investigated the impact of a NAD+-boosting supplement.
Methods
For assessing NAD+ therapy's effects on early-stage ALD, we administered nicotinamide mononucleotide (NMN) at 500 mg/kg through intraperitoneal injection every other day in a 6-week chronic ethanol mouse model (Lieber-DeCarli). Multiple approaches, including RNA-seq, immunoblotting, and metabolomics analysis, were employed to characterize the effects of NMN therapy.
Results
NMN therapy elevated hepatic NAD+ levels, prevented ethanol-induced increases in plasma ALT and AST, and altered the expression of 25% of genes affected by ethanol metabolism. These genes were associated with various pathways, including the MAPK pathway. Notably, NMN treatment normalized Erk1/2 signaling and prevented overexpression of Atf3.
Conclusions
The findings uncover novel mechanisms through which NMN supplementation influences hepatic gene expression and protein pathways, impacting ethanol-induced liver damage in early-stage ALD. This data suggests the need for further research to comprehensively understand treatment approaches and the biochemical implications of NAD+-based interventions.