Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health. 1. Introduction Serum paraoxonase 1 (PON1) is a 45？kDa glycoprotein which can catalyze the hydrolysis of various organophosphates and nerve agents [1, 2] and also metabolize some drugs and prodrugs by its lactonase activity [3]. This enzyme which is located on high density lipoprotein (HDL) particles protects low density lipoprotein (LDL) phospholipids against oxidation [4]. Decreased PON1 activity has been addressed in several diseases such as coronary artery diseases (CAD) [5], type I diabetes [6], obesity [7], and renal failure [8]. It is evident that PON1 activity is influenced by a variety of agents like environmental, pharmacological, and lifestyle factors as well as age and sex [2, 5, 9–11]. Dietary fats have been suggested as an important relevant factor [12, 13]. Studies have presented that dietary fatty acids may affect PON1 activity [14]. Polyenoic fatty acids have shown considerable inhibitory effect on PON1 activity [15], while monoenoic acids (especially oleic acid) protect PON1 from oxidative inactivation [16]. It has been also indicated that replacement of dietary saturated fats with trans fats in healthy men and women leads to a small reduction in the serum PON1 activity [17]. Serum PON1 is almost exclusively found in association with HDL particles. The lipid
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