Nicotinic acid riboside maintains NAD⁺ homeostasis and ameliorates aging-associated NAD⁺ decline.

ABSTRACT: Liver-derived circulating nicotinamide from nicotinamide adenine dinucleotide (NAD⁺) catabolism primarily feeds systemic organs for NAD⁺ synthesis. We surprisingly found that, despite blunted hepatic NAD⁺ and nicotinamide production in liver-specific nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion mice (liver-specific knockout [LKO]), circulating nicotinamide and extra-hepatic organs' NAD⁺ are unaffected. Metabolomics reveals a massive accumulation of a novel molecule in the LKO liver, which we identify as nicotinic acid riboside (NaR). We further demonstrate cytosolic 5'-nucleotidase II (NT5C2) as the NaR-producing enzyme. The liver releases NaR to the bloodstream, and kidneys take up NaR to synthesize NAD⁺ through nic

SUBMITTER: Song WS 

PROVIDER: S-EPMC12328062 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature