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Abstract
Serum paraoxonase 1 (PON1) function has been associated with human cardiovascular disease. The projected mechanism postulates interaction of PON1 with lipoproteins and insulin signaling resulting in alterations in lipid homeostasis. Recently, PON2 was shown to directly regulate triglyceride accumulation in macrophages and PON1 was detected in the interstitial space of adipocytes. The aims of the present study were a) to examine the relationship of the PON1 function with serum parameters related to lipid homeostasis, and b) to examine a possible role of PON1 in the regulation of lipid composition in the human adipose tissue. Two important genetic variations with functional impact on PON1 activity in humans are the Q192R and the L55M. The present study evaluated the impact of the Q192R and the L55M polymorphisms in a cross-section of the population on the island of Crete, as regards to PON1 activity, plasma lipids/lipoproteins, parameters of the metabolic syndrome, and the fatty acid composition of the adipose tissue. We detected a significant association of the polymorphisms with blood pressure, fasting blood glucose, triglycerides, apolipoprotein B, serum iron, and homocysteine. Furthermore, a novel function is suggested for PON1 on the fatty acid composition in the adipose tissue through the positive association of the R allele with saturated fatty acid and of the Q allele with 20:5n3 fatty acid deposition.
Highlights
Serum paraoxonase 1 (PON1) function has been associated with human cardiovascular disease
When analyzing the blood pressure values, we identified a significant association of the L55M genotype with both the systolic blood pressure (SBP) (P = 0.007) and the diastolic blood pressure (DBP) (P = 0.003)
The present study described a preferential reduction of saturated fatty acid (SFA) accumulation in adipose tissue associated with the PON1 Q allele and a reduction of 20:5n3 (EPA) fatty acids associated with the R allele
Summary
Serum paraoxonase 1 (PON1) function has been associated with human cardiovascular disease. The aims of the present study were a) to examine the relationship of the PON1 function with serum parameters related to lipid homeostasis, and b) to examine a possible role of PON1 in the regulation of lipid composition in the human adipose tissue. The present study evaluated the impact of the Q192R and the L55M polymorphisms in a cross-section of the population on the island of Crete, as regards to PON1 activity, plasma lipids/lipoproteins, parameters of the metabolic syndrome, and the fatty acid composition of the adipose tissue. Significant interindividual variability of human serum PON1 activity has been described This variability today is attributed partly to the presence of polymorphisms in the PON1 gene. The PON1 leucine/methionine substitution at the position 55 of the amino acid sequence seems to significantly affect the PON1 serum concentration [10]
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