Relation of protein glycation, oxidation and nitration with osteocalcin level in obese subjects
Carboxylated osteocalcin (Gla-OC) contributes to bone formation whereas the undercarboxylated form (Glu-OC) takes part in energy metabolism. In vitro studies presented that advanced glycation end product-modified bovine serum in osteoblast-like cells resulted in a reduced synthesis of collagen 1 and osteocalcin. The aim of the study was to find association between Gla-OC and markers of protein glycation, oxidation and nitration as well as pro-inflammatory and antioxidant defence markers in obese subjects. Non-obese [(body mass index (BMI)<30 kg/m2; n=34)] and obese subjects (30<BMI <40 kg/m2; n=98), both sexes, aged 25 to 65 years, were included in the study. Urinary glycation, oxidation and nitration free adduct concentrations were determined by stable isotopic dilution analysis liquid chromatography mass spectrometry and normalized to creatinine. Obese subjects had lower serum Gla-OC compared to non-obese controls. Obese subjects had increased serum concentrations of insulin, C reactive protein, interleukin 6, leptin and insulin resistance index (HOMA IR). Urinary early glycation and advanced glycation endproduct (AGE) free products, Nε-fructosyl-lysine and 3-deoxyglucosone-derive hydroimidazolone respectively, and oxidative damage marker, N-formylkynurenine free adduct, were increased in obese compared to non-obese subjects. Serum Gla-OC was correlated negatively with urinary methylglyoxal-derived AGE, hydroimidazolone MG-H1, and N-formylkynurenine free adducts. The index Gla-OC/Glu-OC correlated negatively with MG-H1 free adduct and positively with antioxidant defence marker - glutathione peroxidase activity. Our results suggest that increased AGEs and protein oxidative damage markers in obesity may contribute to decreased Gla-OC level and, consequently, future risk of decreased bone formation.
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