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. Author manuscript; available in PMC: 2022 Jan 11.
Published in final edited form as: Nat Metab. 2020 Nov 16;2(11):1284–1304. doi: 10.1038/s42255-020-00298-z

Fig. 8. Blocking CD38 extracellular enzymatic activity regulates NMN, NAD+ levels, and CD38 activity in vivo.

Fig. 8.

(a-c) 4 month-old WT and CD38 KO mice were treated with vehicle (Ctrl), Ab68 (5 mg/kg), or Ab69 (5 mg/kg) by intraperitoneal (i.p.) injection on day 1 and day 5, and euthanized on day 8. (a) Relative CD38 activity in WAT. Levels are relative to control WT (Ctrl) (WT Ctrl n=6; WT Ab68, CD38 KO n=5; WT Ab69 n=3 mice). (b) NAD+ levels in WAT (WT n=4 mice; CD38 KO n=5 mice). (c) Heat map showing levels of metabolites in WT mice treated with Ab68 and Ab69 relative to Ctrl (n=4 mice per group). (d) 4 month-old WT mice were treated withFK866 (FK) (25 mg/kg) and/or Ab68 (5 mg/kg) (n=5 mice per group). NMN and NAD+ levels were measured in WAT. Levels are relative to Ctrl. (e) 22 month-old WT mice were injected i.p. with a single dose of vehicle (Ctrl) or Ab68 (5 mg/kg), euthanized at different time points, and NMN and NAD+ levels measured in WAT. Graphs show the time course of the relative increase of NMN or NAD+ in vehicle and Ab68-treated over levels at time 0 (n=4 mice per group). (f) 18 month-old mice were injected i.p. with a single dose of vehicle (Ctrl) or Ab68 (5 mg/kg) and mice were euthanized at different time points. NMN levels were measured in serum (Ctrl, 0, 24, 72 hours, and Ab68 72 hours n=4 mice per group; Ab68 24 hours n=5 mice; Ctrl 6 hours n=8 mice; Ab68 6 hours n=9 mice). (g) 18 month-old WT mice were injected i.p. with vehicle (Ctrl, NMN groups), 5 mg/kg Ab68 (Ab68, Ab68+NMN groups), with and without 500 mg/kg NMN. Serum NMN levels were determined (n=5 mice per group). (h) Absolute NAD+ levels in WAT of 3 month-old (young) and 18 month-old (old) mice were determined 3 days after treatment with a single injection i.p. injection of vehicle (Ctrl) or 5 mg/kg Ab68 (n=5 mice per group). (i) 3 month old and 18 month-old mice were treated with Ab68 and NMN as described in panel (g) and WAT levels of NAD+ were measured. NAD+ levels after each treatment are expressed relative to its age-matched control (vehicle treatment) (n=5 mice per group). Data are mean ± SEM, analyzed by unpaired two-sided t-test, except for (e-f) where data are analyzed by two-way ANOVA.