PPARα L162V polymorphism alters the potential of n‐3 fatty acids to increase lipoprotein lipase activity

Abstract

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.

The role of dietary fatty acids in the pathology of metabolic syndrome

“…In addition, as they are involved in important transcriptional regulatory pathways, they increase PPAR-α, which regulates lipoprotein lipase (LPL) synthesis [38]. They also modulate genes involved in lipogenesis, together with nuclear receptors and transcription factors, including PPAR-γ, hepatocyte nuclear factor 4α (HNF-4α), LXR and nuclear factorkappa B (NF-κB) [46,37]. Therefore, they increase fatty acid oxidation by PPAR-α activation or by reducing SREBP activity, inhibiting lipogenesis [39,40].…”

“…These unsaturated long-chain ω-3 fatty acids influence the physical properties of membranes (e.g., fluidity, thickness and deformability) and, consequently, interfere with transmembrane protein activity [34]. They are related to the moderate reduction of triacylglycerols by impairing diacylglycerol acyltransferase activity, which is critical in hepatic triacylglycerol synthesis [35], thus decreasing hepatic VLDL secretion [36], but high doses may adversely decrease LDL receptor and produce small LDL, which is related to atherosclerosis [37]. In addition, as they are involved in important transcriptional regulatory pathways, they increase PPAR-α, which regulates lipoprotein lipase (LPL) synthesis [38].…”

Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity

“…For example, in vitro studies demonstrated that the effects of omega-3 fatty acids supplementation on plasma triglyceride clearance through increasing transcription rates of lipoprotein lipase (LPL) gene, were dependent on the L162V polymorphism in the peroxisome proliferator-activated receptor alpha ( PPARA ) gene [102]. Another study reported that gene expression levels of PPARA and apolipoprotein A1 ( APOA1 ) were influenced by the PPARA L162V polymorphism after the supplementation of omega-3 fatty acids [103].…”

Associations between Polymorphisms in Genes Involved in Fatty Acid Metabolism and Dietary Fat Intakes

“…In spite of its functional significance [18], the PPAR α Leu162Val was not associated with dietary fat intakes. These results are in accordance with those of Robitaille et al [19].…”

“…One missense mutation has been identified at codon 162 (Leu162Val) which results in the substitution of a leucine for a valine [17]. This mutation results in a lower transcriptional activity and a deteriorated metabolic profile for carriers of the Val162 allele [17,18,19]. PPAR γ is mostly expressed in adipose tissue and is involved in adipocyte differentiation [20].…”