Figure 7. NR contributes directly to hepatic NAAD.

Double-labelled NR was orally administered to mice. At indicated times after gavage, mice (n=3) were euthanized and livers freeze-clamped for isotopic enrichment analysis. Data are plotted as pmol mg⁻¹ of wet tissue weight. At the 2 h time point, hepatic NAD⁺ (a) shows 54% incorporation of M+1 and M+2 species, indicating that more than half of the NAD⁺ is turned over before there is a rise in steady-state NAD⁺. At 2 h, hepatic NADP⁺ (b) shows 32% incorporation of label(s) from ingested NR. At all time points, half or more of hepatic Nam (c) and MeNam (d) carries an NR-derived label, indicating that NR has driven rapid NAD⁺ synthesis and consumption. At 2 h after gavage, 45% of hepatic NAAD (e) incorporates NR-derived label(s). At 2 h, hepatic NAD⁺ (a), NADP⁺ (b) and NAAD (e) pools incorporate 5, 6 and 8% of double-labelled NR indicating that NR is a direct precursor of all three metabolites and excluding the possibility that the NR-driven increase in NAAD is due to inhibition of de novo synthesis.