Female PPARα and CYP2A5 double knockout mice (P-A- mice), their female littermates not expressing CYP2A5 but expressing PPARα (P+A-) or expressing CYP2A5 but not expressing PPARα (P-A+), were fed HFD or CD for 10 weeks. While P+A- mice (equivalent to cyp2a5−/− mice) developed severe obesity (Fig. 3A middle panel), surprisingly, body weight in P-A- mice (Fig. 3A left panel) and P-A+ mice (equivalent to Pparα−/− mice) (Fig. 3A right panel) was not significantly increased in response to HFD feeding. Adipose tissue section H&E staining showed that sizes of adipocyte in P+A- mice were larger than those in P-A- mice and P-A+ mice (Fig. 3B). Although there was no difference in serum insulin levels among P-A- mice, P+A-mice and P-A+ mice (Supplemental Fig. 2A), P+A- mice exhibited more severe glucose intolerance (Fig. 3C middle panel) than P-A- mice (Fig. 3C left panel) and P-A+ mice (Fig. 3C right panel); HFD feeding worsen the glucose intolerance in P+A- mice but HFD had no effect on glucose intolerance in P-A- mice and P-A+ mice (Fig. 3C). Pyruvate tolerance test showed that blood glucose
