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adipose tissue; evolution and distribution of APOE alleles; lipid deposition and mobilization; mitochondrial fatty acid oxidation; skeletal muscle
Abstract:
Scope: Of the three human apolipoprotein E (APOE) alleles, the ε 3 allele is most common,
which may be a result of adaptive evolution. In this study, we investigated whether the APOE
genotype affects body weight and energy metabolism through regulation of fatty acid utilization.
Methods and results: Targeted replacement mice expressing the human APOE3 were significantly
heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat
feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3mice.
Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma
nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4
mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in
skeletal muscle.
Conclusion: Our data suggest that APOE3 is associated with the potential to more efficiently
harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase
fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The
different handling of dietary energy may have contributed to the evolution and worldwide
distribution of the ε3 allele.
