Crosstalk Between Adipokines and Paraoxonase 1: A New Potential Axis Linking Oxidative Stress and Inflammation.
Veronica TisatoArianna RomaniElisa TavantiElisabetta MelloniDaniela MilaniGloria BonaccorsiJuana Maria Sanz MolinaDonato GemmatiAngelina PassaroCarlo CervellatiPublished in: Antioxidants (Basel, Switzerland) (2019)
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.
Keyphrases
- poor prognosis
- oxidative stress
- postmenopausal women
- cardiovascular disease
- growth factor
- metabolic syndrome
- insulin resistance
- binding protein
- high density
- type diabetes
- bone mineral density
- weight loss
- coronary artery disease
- transcription factor
- dna damage
- weight gain
- rheumatoid arthritis
- physical activity
- long non coding rna
- single cell
- skeletal muscle
- small molecule
- climate change
- high fat diet induced
- low density lipoprotein
- heat shock