Fig. 6: NAMPT induces SIRT1-dependent hepatic FGF21 and selectively enhances energy metabolism.

A Body weights over time in WT and SIRT1^LKO mice overexpressing empty vector or NAMPT on 12wk Western diet. n = 3 SIRT1^fl/fl Chow; 9 SIRT1^fl/fl EV WD; 6 SIRT1^fl/fl AAV8-NAMPT WD; 5 SIRT1^LKO EV WD. B–D 4 h fasting glucose, insulin, and HOMA-IR (homeostatic model of insulin resistance − fasting glucose (mg/dL) × fasting insulin (ng/mL)/405) in WT and SIRT1^LKO mice overexpressing vector or NAMPT after 12wk chow or Western diet feeding. n = 4 SIRT1^fl/fl Chow; 11 SIRT1^fl/fl EV WD; 4 SIRT1^LKO EV WD; 6 SIRT1^LKO AAV8-NAMPT WD. E FGF21 mRNA and serum peptide, as quantified by qRT-PCR in livers and by serum ELISA in WT and SIRT1^LKO mice overexpressing empty vector or NAMPT after Western diet feeding. Interaction, P < 0.01 and <0.05 for FGF21 mRNA and peptide, respectively. n = 4 SIRT1^fl/fl Chow; 11 SIRT1^fl/fl EV WD; 6 SIRT1^fl/fl AAV8-NAMPT WD; 4 SIRT1^LKO EV WD; 6 SIRT1^LKO AAV8-NAMPT WD (F). Indirect calorimetry in WT and SIRT1^LKO mice overexpressing vector or NAMPT after 12wk chow or Western diet feeding. n = 3 SIRT1^fl/fl Chow; 6 SIRT1^fl/fl EV WD; 6 SIRT1^fl/fl AAV8-NAMPT WD; 4 SIRT1^LKO EV WD; 5 SIRT1^LKO AAV8-NAMPT WD. Interactions for light and dark cycle heat: P = ns, and P < 0.01 respectively. *, **, P < 0.05, <0.01 vs. bracketed control by Tukey’s multiple comparisons testing. Error bars in (A–F) represent SEM. Circles, SIRT1^fl/fl Chow; Squares, SIRT1^fl/fl EV WD; Upward Triangles SIRT1^fl/fl AAV8-NAMPT WD; Downward Triangles, SIRT1^LKO EV WD; Diamonds SIRT1^LKO AAV8-NAMPT WD. Statistical tests: (A), repeated measures ANOVA. B–D one-way ANOVA with Dunnett’s post hoc testing. E, F Two-way ANOVA, Tukey’s post hoc correction.