Abstract
Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated protein that endows its carrier with (lipo-)lactonase-dependent antioxidative features. Low levels of PON1 activity have been observed in association with obesity, a major risk factor for cardiovascular disease (CVD). Considering the well-recognized atheroprotective role of PON1, exogenous/endogenous factors that might modulate its levels/activity are raising great interest. Since adipokines represent a molecular link between obesity and CVD, we here explored the possible impact of these substances on PON1 activity/expression. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, monocyte chemoattractant protein-1, hepatocyte growth factor, resistin, leptin, and adiponectin were measured along with arylesterase, paraoxonase, and lactonase activities of PON1 in 107 postmenopausal women. Moreover, the direct effect of resistin on PON1 expression was evaluated in vitro. Multivariate analysis revealed that only resistin was significantly and inversely correlated with PON1-lactonase activities (r = −0.346, p < 0.001) regardless of confounding factors such as age or HDL-cholesterol. It is worth noting that no statistical link was found between adipokine and arylesterase or paraoxonase, the two promiscuous activities of PON1. Notably, resistin down-regulated PON1 expression occurred in hepatocellular carcinoma cultures. Our study suggests that resistin might be a negative modulator of PON1 expression and anti-oxidative activity.
Highlights
Paraoxonase 1 (PON1) (E.C. 3.1.8.1) is a member of a family of enzymes secreted by the liver and detectable as circulating molecules in the bloodstream bound to high-density lipoproteins (HDL)Antioxidants 2019, 8, 287; doi:10.3390/antiox8080287 www.mdpi.com/journal/antioxidantsAntioxidants 2019, 8, 287 and, to a minor extent, to other lipoproteins [1,2]
A high content in PON1 appeared to enhance the ability of these lipoproteins to prevent peroxidative damage to low-density lipoproteins (LDL) and cell membranes, and it has been suggested that they may protect against pro-inflammatory activation of macrophages and endothelium [4,5,6]
The main clinical characteristics of the cohort of women enrolled in the study and the levels of the measured adipokines and PON1 activities are shown in Table 1 and Table S1, respectively
Summary
Paraoxonase 1 (PON1) (E.C. 3.1.8.1) is a member of a family of enzymes secreted by the liver and detectable as circulating molecules in the bloodstream bound to high-density lipoproteins (HDL)Antioxidants 2019, 8, 287; doi:10.3390/antiox8080287 www.mdpi.com/journal/antioxidantsAntioxidants 2019, 8, 287 and, to a minor extent, to other lipoproteins [1,2]. Low PON1 activity seems to result in a decreased functional efficiency of HDL, which in turn increases the risk of developing inflammatory diseases, including (but not limited to) atherosclerosis [5,7,8]. The mechanisms linking obesity to clinical presentations involve a self-perpetuating loop between chronic low-grade inflammation and oxidative stress (OxS) [10]. The effect of this axis becomes health-threatening when defensive/compensating mechanisms are affected/impaired. This event occurs for example in the context of obesity, a condition in which antioxidant and anti-inflammatory agents are not able to effectively counteract the persistence of a source of toxicants, reactive species, and pro-inflammatory cytokines [11].
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