Abstract
BackgroundBeneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the lipid levels of dyslipidemic subjects are widely described in the literature. However, the underlying molecular mechanisms are largely unknown. The aim of this study was to investigate the effects of n-3 PUFAs on the expression of lipid metabolism-related genes in normo- and dyslipidemic men to unveil potential genes and pathways affecting lipid metabolism.MethodsTen normo- and ten dyslipidemic men were supplemented for twelve weeks with six fish oil capsules per day, providing 1.14 g docosahexaenoic acid and 1.56 g eicosapentaenoic acid. The gene expression levels were determined by whole genome microarray analysis and quantitative real-time polymerase chain reaction.ResultsSeveral transcription factors (peroxisome proliferator-activated receptor α (PPARα), retinoid X receptor (RXR) α, RXRγ, hepatic nuclear factor (HNF) 6, and HNF1ß) as well as other genes related to triacylglycerol (TG) synthesis or high-density lipoprotein (HDL-C) and cholesterol metabolism (phospholipids transfer protein, ATP-binding cassette sub-family G member 5, 2-acylglycerol O-acyltransferase (MOGAT) 3, MOGAT2, diacylglycerol O-acyltransferase 1, sterol O-acyltransferase 1, apolipoprotein CII, and low-density lipoprotein receptor) were regulated after n-3 PUFA supplementation, especially in dyslipidemic men.ConclusionGene expression analyses revealed several possible molecular pathways by which n-3 PUFAs lower the TG level and increase the HDL-C and low-density lipoprotein level, whereupon the regulation of PPARα appear to play a central role.Trial registrationClinicalTrials.gov (ID: NCT01089231)
Highlights
Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 Omega-3 polyunsaturated fatty acid (PUFA)) on the lipid levels of dyslipidemic subjects are widely described in the literature
Studies have repeatedly shown that n-3 PUFAs increase low-density lipoprotein cholesterol (LDL-C) levels, which may result from the conversion of Very low-density lipoprotein (VLDL) to LDL-C [13]
N-3 PUFAs can modulate the activity of several transcription factors, such as sterol regulatory element-binding protein (SREBP) 1 [14], hepatic nuclear factor (HNF) 4α [15], liver X receptors [16], retinoid X receptor (RXR) [17], farnesoid X receptor [18], and peroxisome proliferator-activated receptors (PPARs) [19], resulting in an altered expression of corresponding target genes [20,21,22,23,24]
Summary
Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the lipid levels of dyslipidemic subjects are widely described in the literature. Beyond TG lowering, n-3 PUFAs affect the high-density lipoprotein cholesterol (HDL-C) metabolism by elevating the cholesterol-rich HDL2 subtype and reducing the TGrich HDL3 subtype [11,12] Beside these beneficial effects, studies have repeatedly shown that n-3 PUFAs increase low-density lipoprotein cholesterol (LDL-C) levels, which may result from the conversion of VLDL to LDL-C [13]. It is known that these genes, or rather their products, play eminent roles in the regulation of the lipid metabolism, the influence of n-3 PUFAs on a number of additional lipid metabolismrelated genes and involved pathways remain to be discovered Unravelling these connections may contribute to the understanding of the molecular mechanisms explaining the physiological functions of n-3 PUFAs
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