Study of the potential influence of obesity on the activities of serum Paraoxonase-1 and lipoprotein-associated phospholipase A2

INTRODUCTION: Obesity is independently associated with disturbances in lipid and lipoprotein metabolism, oxidative stress and is a well-established independent risk factor cardiovascular diseases (CVD) [1]. Human paraoxonase 1 (PON1) is a pleotropic high density lipoprotein (HDL)-associated enzyme with antioxidant and anti-inflammatory proprieties which have been suggested to contribute to the athero-protective function of the lipoprotein [2]. In contrast, lipoprotein-associated phospholipase A2 (Lp-PLA2) is prevalently bound to low density lipoprotein (LDL) and might act as a pro-atherogenic player. This study aimed to explore whether and in which extent PON1 and Lp-PLA2 are associated with obesity and, thus, could act as mediators of the adverse effects of this condition on cardiovascular health [3]. METHODS: The serum activities of these two enzymes were spectrophotometrically measured in 101 obese and severely obese, 101 overweight and 129 normal-weight women (controls) women (mean age: 54, intequartile range: 48-61). Markers of inflammation (high-sensitivity-C-reactive protein, hs-CRP) and oxidative stress (hydroperoxides), and lipid profile were also assessed. RESULTS: PON1 activity showed significant differences across the BMI groups (ANOVA, p<0.01), with the greatest decrease (almost 20%) observed in subjects with body mass index (BMI)> 40kg/m2 compared to controls (p<0.001). PON1 and lp-PLA2 were both significantly associated to BMI but with opposite directions (negative, r= -0.280, p<0.01 and positive, r=201, p<0.05, respectively). At the multivariate analysis, PON1 emerged to be correlated with BMI in a way independent of age, inflammation and oxidative stress, thus suggesting that other factors may mediate the link between the enzyme expression/activity and obesity. CONCLUSIONS: our data suggest that lower PON1 and/or higher lp-PLA2 activities might contribute to increase the risk of cardio-metabolic disorders in obese women. 1. Keaney JF, et al. Arterioscler Thromb Vasc Biol. 2003;23(3):434–9. 2. Cervellati C, et al. 2016;64(1):21–32. 3. Tellis CC, Tselepis AD. Biochim Biophys Acta. 2009 May;1791(5):327–38.