CO Improves Mitochondrial Population Figure 2. Effects of CORM-3 on metabolic parameters. (A) Oral glucose tolerance and (B) insulin tolerance tests were performed on ND (black circles), ND + CORM-3 (black triangles), HFD (black squares) and HFD + CORM-3 (white diamonds) mice. Data are means 6 SEM. n = 10 in each group. (a) p,0.05 between HFD and ND; (b) p,0.05 between HFD + CORM-3 and ND. (C) Plasma cholesterol and (D) true triglyceride measurements were performed on 6–10 different samples in each group. Data are means 6 SEM. (E) Basal oxygen uptake (VO2) and carbon dioxide rejection (VCO2), (F) respiratory exchange ratio (RER). Data represent means 6 SEM. n = 5–7 in each group, * p,0.05 vs. ND. White bars = ND; vertically hatched bars = ND + CORM-3; black bars = HFD; crosshatched bars = HFD + CORM-3. doi:10.1371/journal.pone.0041836.g002 Then, we measured oxygen uptake (VO2) and carbon dioxide rejection (VCO2) in mice under basal condition. While no differences in VCO2 were observed between the three groups (Figure 2E), mice fed with HFD consumed more oxygen than ND mice (Figure 2E). CORM-3 injection did not modify oxygen uptake (Figure 2E). As a consequence, HFD and HFD + CORM-3 mice used preferentially lipids as their respiratory exchange ratios (RER) were close to 0.7 (Figure 2F). On the contrary, RER value of ND mice was about 0.8, indicating that relative substrate utilization between lipids and carbohydrates was different from PLoS ONE | www.plosone.org 5 August 2012 | Volume 7 | Issue 8 | e41836