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Chunk #21 — RESULTS — PPARα absence in cyp2a5−/− mice blunts HFD-induced obesity but enhances HFD-induced fatty liver

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CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model.
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While HFD-induced obesity was suppressed in P-A- mice, HFD-induced fatty liver was more pronounced in P-A- mice than in P+A- mice and P-A+ mice, even CD-fed P-A- mice exhibited a weak steatosis but CD-fed P+A- mice or P-A+ mice did not (Fig. 4A). Immunohistochemistry staining indicates that most lipid droplets were surrounded by ADRP (Supplemental Fig. 3). Sirius Red staining showed that HFD-induced collagen fiber was mainly located in sinusoids (Supplemental Fig. 4). There were no significant differences in serum levels of triglyceride and aspartate transaminase (ALT) between P-A- mice and P+A- mice (Supplemental Fig. 2B, 2C). Although serum glycerol, a marker of adipolysis, had no significant difference among the groups (Supplemental Fig. 2D), serum free fatty acids, which are mainly derived from adipose tissue after an overnight fasting, was lower in P+A- mice than in P-A- mice and P-A+ mice (Fig. 4B),. Serum β-hydroxylbutyrate, indicative of ketogenesis, was lower in P-A- mice and P-A+ mice than in P+A- mice (Fig. 4C).