Alteration of PON1 activity in adult and childhood obesity and its relation to adipokine levels.
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 above-mentioned 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.
Seres
Ildikó
I
Department of Internal Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary. seres@internal.med.unideb.hu
Bajnok
László
L
Harangi
Mariann
M
Sztanek
Ferenc
F
Koncsos
Peter
P
Paragh
György
G
D054392:Adipokines / Q000378:metabolism*; D000328:Adult; D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D050197:Atherosclerosis; D002648:Child; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020738:Leptin / Q000378:metabolism; D015227:Lipid Peroxidation; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic; D017392:Thiobarbituric Acid Reactive Substances
D054392:Adipokines; D020738:Leptin; D017392:Thiobarbituric Acid Reactive Substances; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human