Crosstalk Between Adipokines and Paraoxonase 1: A New Potential Axis Linking Oxidative Stress and Inflammation
Veronica Tisato,
Arianna Romani,
Elisa Tavanti,
Elisabetta Melloni,
Daniela Milani,
Gloria Bonaccorsi,
Juana M. Sanz,
Donato Gemmati,
Angelina Passaro,
Carlo Cervellati
Affiliations
Veronica Tisato
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Arianna Romani
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy
Elisa Tavanti
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Elisabetta Melloni
Department of Biomedical and Specialist Surgical Sciences and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Daniela Milani
Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
Gloria Bonaccorsi
Department of Morphology, Surgery and Experimental Medicine, Menopause and Osteoporosis Centre, University of Ferrara, 44121 Ferrara, Italy
Juana M. Sanz
Department of Medical Sciences, Internal Medicine and CardioRespiratory Section, University of Ferrara, 44121 Ferrara, Italy
Donato Gemmati
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics-Ctr. Hemostasis & Thrombosis, University of Ferrara, 44121 Ferrara, Italy
Angelina Passaro
Department of Medical Sciences, Internal Medicine and CardioRespiratory Section, University of Ferrara, 44121 Ferrara, Italy
Carlo Cervellati
Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy
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.