Alteration of PON1 Activity in Adult and Childhood Obesity and Its Relation to Adipokine Levels

Abstract

Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows an increasing incidence in the industrialized countries. Adipokines such as leptin, adiponectin and resistin have a great impact on the development of atherosclerosis in obesity. Elevated levels of leptin have been found to be atherogenic whereas decreased levels of adiponectin have been proved to be anti-atherogenic in recent studies. The exact role of resistin in the process of atherosclerosis has so far remained uncertain and controversial. In our recent work, we studied the alteration in human paraoxonase-1 (PON1) activity and adipokine levels; furthermore, we also aimed at identifying the potential correlation between these parameters in this metabolic disorder. We investigated the abovementioned parameters both in adults and in children, with regard to the emerging role of childhood obesity and to get a clearer view of these factors during a whole lifetime. Investigating the adult population with a broad range of body mass index (BMI) we found significantly increased leptin and significantly decreased adiponectin and resistin levels and PON1 activity in the obese group compared to the lean controls. Adiponectin and resistin levels showed significantly positive correlation, while leptin and BMI showed significantly negative correlation with PON1 activity.Our findings were similar in childhood obesity: leptin showed significantly negative correlation, while adiponectin showed significantly positive correlation with PON1 activity. We found gender differences in the univariate correlations of leptin and adiponectin levels with PON1 activity in the adult population. In multiple regression analysis, adiponectin proved to be an independent factor of PON1 activity both in childhood and adult obesity, furthermore thiobarbituric acid-reactive substances (TBARS) also proved to be an independent predictor of the enzyme in adults, reflecting the important role of oxidative stress in obesity. Investigating PON 192 Q/R polymorphism by phenotypic distribution (A/B isoenzyme) in obese children, we found a significant correlation of PON1 arylesterase activity with leptin and adiponectin levels, and of body fat percentage with PON1 192 B isoenzyme.According to our studies, these metabolic changes in obesity predispose to the early development of atherosclerosis throughout our whole lifetime. Decreased activity of PON1 and alterations in adipokine levels in childhood obesity could contribute to an early commencement of this process, detected only later in adulthood by increased cardiovascular morbidity and mortality. Changed levels of leptin, adiponectin, resistin and PON1 activity at all ages, just like 192 Q/R polymorphism determined by phenotypic distribution, may be useful markers beside the general risk factors.Keywords (separated by '-') Adipokines -Leptin -Adiponectin -Resistin -Obesity -Paraoxonase-1 -Childhood Abstract Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows a...

Effect of Red Wine Consumption on Serum Oxidation and Adiponectin Levels in Overweight and Healthy Individuals

“…Our data is consistent with fi ndings of other studies Seres et al, 2010] that showed that adiponectin proved to be an independent factor of PON1 activity in both childhood and adult obesity.…”

Identification of anti-adipogenic proteins in adult bovine serum suppressing 3T3-L1 preadipocyte differentiation

“…In addition, it was demonstrated that a PON1 variant, PON2, attenuates the accumulation of triglycerides in mouse macrophages by reducing intracellular oxidative stress and inhibiting diacylglycerol acyl transferase (11). These previous results explain another previous report in which serum PON1 activity was shown to be negatively related with obesity (12). Consistently, the results of this study showed that PON1, an ABS-specific protein, may have an anti-adipogenic effect by decreasing oxidative stress during the differentiation of preadipocytes.…”

“…2 with an oval) were identified as peptides derived from immunoglobulins, which are supposed to be involved in immune responses. However, two protein spots were identified to as alpha-2-macroglobulin (A2M) and paraoxonase/arylesterase 1 (PON1), which were previously reported to suppress adipocyte differentiation (9,11,12). Therefore, A2M and PON1 were further analyzed with ABS, FBS, and fractionated serum proteins.…”

Associations of PON1 and Genetic Ancestry with Obesity in Early Childhood

“…Obesity, in particular, is considered a condition of chronic oxidative stress[19]. Data on the relationship between PON1 and obesity, especially in children, are limited[20]. In adults, a few small studies have reported a trend of lower PON1 activity in obese versus normal weight individuals[21], [22], [23].…”