Omega‐3 fatty acids regulate gene expression levels differently in macrophages of men carrying the PPARα‐L162V polymorphism

Abstract

Omega‐3 fatty acids (FAs) are natural ligands of the peroxisome proliferator‐activated receptor‐α (PPARα), a nuclear receptor that modulates expression levels of genes involved in lipid metabolism. The L162V polymorphism located in the ligand binding domain of the PPARα gene is associated with a deteriorated plasma lipid profile. Therefore, we postulate that subjects carrying the V162 allele exhibit differences in the activation of PPARα and its target genes after incubation with omega‐3 FAs compared with L162 homozygotes. Peripheral blood monocytes from 6 men carrying the V162 allele paired for age and for body mass index with 6 L162 homozygotes were differentiated into macrophages and incubated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or mixtures of EPA: DHA. Results demonstrate that gene expression levels of PPARα and apolipoprotein AI were significantly lower for carriers of the V162 allele compared to L162 homozygotes after the addition of DHA and a mixture of EPA: DHA. Additionally, lipoprotein lipase expression displayed a tendency to be lower in carriers of the V162 allele after the addition of a mixture of EPA: DHA. Consequently, subjects bearing the PPARα V162 allele may demonstrate inferior improvements in the plasma lipid profile due to lower PPARα and its target genes expression rates in response to omega‐3 FA supplementation. Funding provided by a CIHR Operating Grant.