## 3 Results  
Effect of Supplementation with NR on Weekly Food and Energy Intaks and Final Body Weights in CD- or HFD-Fed ApoE-/- Mice  
During 12 weeks of treatment, although the weekly food intakes in ApoE-/- mice were lower in HFD and HFD + NR than the CD and CD + NR groups (_P-diet_ = 0.0183) (Figure 1A), the weekly energy intakes were higher in HFD and HFD + NR than CD and CD + NR groups due to the higher energy density of HFD (_P-diet_ = 0.0058) (Figure 1B). Consequently, the body weights of ApoE-/- mice fed with HFD and HFD + NR were significantly higher than those fed with CD and CD + NR (_P-diet_ = 0.0005) (Figure 1C). Supplementation with NR did not change food and energy intakes or body weights in mice fed with either CD or HFD (Figure 1A-C). Effect of Supplementation with NR on Fasting Blood Concentrations of Biochemical Parameters and Atherosclerosis Lesion Development in CD- or HFD-Fed ApoE-/- Mice  
At the end of the 12-week treatment period, ApoE/- mice fed with HFD and HFD + NR resulted in higher fasting concentrations of plasma TC, HDL-C, non-HDL-C and PCSK9 and ratios of TC to HDL-C and LDL-C to HDL-C compared to mice fed with CD and CD + NR (all _P-diet_ \(<\) 0.05) (Table 1). Supplementation with NR did not change these parameters, and there were no significant differences in TG, LDL-C and VLDL-C concentrations among the four groups. In comparison to HFD, HFD + NR resulted in lower fasting glucose concentrations in ApoE/- mice (_P-diet*NR_ = 0.0011, _P-diet_ \(<\) 0.0001) (Table 1). The percentage of atherosclerotic lesions as stained by Oil Red O of the entire aorta was higher in mice fed with HFD and HFD + NR in comparison to the mice fed with CD and CD + NR (_P-diet_ \(<\) 0.0001) (Figure 2), with no significant effect from NR supplementation. \begin{table}
\begin{tabular}{l c c c c c c c} \hline
**Variables** & **CD** & **CD + NR** & **HFD** & **HFD + NR** & _P-Diet_ & _P-NR_ & _P-Diet*NR_ \\ \hline TC, mmol/L & \(22.5\pm 1.5\)b & 24.9 \(\pm\) 1.8b & 40.2 \(\pm\) 2.3a & 37.0 \(\pm\) 4.5a & \(<\)0.0001 & 0.89 & 0.33 \\ HDL-C, mmol/L & \(1.0\pm 0.1\)b & \(1.1\pm 0.0\)b & \(1.3\pm 0.1\)a & \(1.4\pm 0.1\)a & \(<\)0.0001 & 0.07 & 0.97 \\ non-HDL-C, mmol/L & \(21.5\pm 1.5\)b & 23.7 \(\pm\) 1.8b & 38.8 \(\pm\) 2.3a & 35.6 \(\pm\) 4.4a & \(<\)0.0001 & 0.87 & 0.33 \\ TC: HDL-C & \(21.0\pm 2.1\)b & \(21.9\pm 1.3\)b & \(29.2\pm 2.9\)a & \(26.3\pm 3.0\)a & 0.0139 & 0.68 & 0.44 \\ LDL-C: HDL-C & \(7.1\pm 0.8\)b & \(7.6\pm 0.5\)b & \(10.4\pm 1.1\)a & \(9.0\pm 1.1\)a & 0.0315 & 0.20 & 0.26 \\ TG, mmol/L & \(1.2\pm 0.2\) & \(1.3\pm 0.2\) & \(1.6\pm 0.2\) & \(1.5\pm 0.1\) & 0.21 & 0.87 & 0.76 \\ LDL-C, mmol/L & \(7.6\pm 0.6\) & \(8.6\pm 0.7\) & \(14.4\pm 0.8\) & \(12.6\pm 1.6\) & 0.24 & 0.34 & 0.40 \\ VLDL-C, mmol/L & \(0.6\pm 0.1\) & \(0.6\pm 0.1\) & \(0.7\pm 0.1\) & \(0.7\pm 0.1\) & 0.21 & 0.85 & 0.76 \\ Glucose, mmol/L & \(4.3\pm 0.2\)c & \(5.0\pm 0.1\)bc & \(6.9\pm 0.5\)a & \(5.6\pm 0.2\)b & \(<\)0.0001 & 0.31 & 0.0011 \\ PCSK9, ng/mL & \(3.1\pm 0.5\)b & \(3.0\pm 0.5\)b & \(12.1\pm 2.4\)a & \(16.0\pm 5.8\)a & \(<\)0.0001 & 0.74 & 0.77 \\ \hline \end{tabular}  
* Data were presented as mean \(\pm\) SEM. A statistical analysis was performed using a two-way analysis of variance (ANOVA) with the main effects of diet and NR and diet*NR interaction. _P-diet_ indicated significant main effect of diet (HFD vs. CD), _P-N_ indicated significant main effect of NR supplementation (NR supplementation vs. no supplementation), and _P-diet*NR_ indicated significant interaction between diet and NR supplementation. Means with different letters (a, b or c) indicated a significant difference from each other. CD (control), n = 10; CD + NR, n = 11; HFD, n = 10; HFD + NR, n = 10. CD, control diet; HDL-C, HDL-cholesterol; HFD, high-fat and high-cholesterol diet; LDL-C, LDL-cholesterol; non-HDL-C, non-HDL-C, non-HDL-C, postKS9, Prov protein converse subtilisian/kexin type 9; total cholesterol; TG, triglyceride; VLDL-C, VLDL-cholesterol; + NR, a diet plus oral gavage with 0.3 g/kg/kg/day of NR.  
\end{table}