PPARalpha L162V polymorphism alters the potential of n-3 fatty acids to increase lipoprotein lipase activity.
Omega-3 fatty acids (FAs) may accelerate plasma triglyceride (TG) clearance by altering lipoprotein lipase (LPL) activity. Yet, the ability of n-3 FAs to increase LPL activity is dependent on transcription factors such as peroxisome proliferator-activated receptor alpha (PPARalpha). The objective was to examine the effects of n-3 FAs on LPL activity considering the occurrence of PPARalpha L162V polymorphism. First, 14 pairs of men either L162 homozygotes or carriers of the V162 allele were supplemented with n-3 FAs. Second, transient transfections in HepG2 cells, for the L162- and V162-PPARalpha variants with the peroxisome proliferator-response element from the human LPL gene, were transactivated with n-3 FAs. In vivo results demonstrate that the LPL activity increased non-significantly by 14.4% in L162 homozygotes compared with 6.6% in carriers of the PPARalpha-V162 allele, after n-3 FA supplementation. Additionally, the L162 homozygotes tended towards an inverse correlation between LPL activities and plasma TG levels. Conversely, carriers of the V162 allele showed no such relationship. In vitro data demonstrates that transcription rates of LPL tended to be higher for the L162-PPARalpha than V162-PPARalpha after n-3 FAs activation. Overall, these results indicate that n-3 FA supplementation increases the transcription rate of LPL to a greater extent in L162-PPARalpha than V162-PPARalpha.
Rudkowska
Iwona
I
Lipid Research Center, CHUL Research Center, Sainte-Foy, Québec, Canada.
Caron-Dorval
Dominique
D
Verreault
Mélanie
M
Couture
Patrick
P
Deshaies
Yves
Y
Barbier
Olivier
O
Vohl
Marie-Claude
MC
D000293:Adolescent; D000328:Adult; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004032:Diet; D004281:Docosahexaenoic Acids / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000097:blood; D004912:Erythrocytes / Q000737:chemistry; D005227:Fatty Acids / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood* / Q000235:genetics; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014162:Transfection
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008055:Lipids; D047493:PPAR alpha; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D008071:Lipoprotein Lipase