HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Beltowski, J. Articles by Jakubowski, H. PubMed PubMed Citation Articles by Beltowski, J. Articles by Jakubowski, H.

J Beltowski, University of Medicine, Department of Pathophysiology, Lublin, 20-950 , Poland
G Wojcicka, Dept. of Pathophysiology, Medical University, Lublin, Poland
H Jakubowski, Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, International Center for Public Health, Newark, United States

Correspondence: Jerzy Beltowski, Email: jerzy.beltowski{at}am.lublin.pl

The adipose tissue hormone leptin and homocysteine (Hcy)-thiolactone are linked to the pathogenesis of atherosclerosis through their interactions with the anti-atherogenic enzyme paraoxonase 1 (PON1) which has the ability to hydrolyze Hcy-thiolactone and minimize protein N-homocysteinylation. Here we examined relationships between hyperleptinemia, Hcy-thiolactonase, and protein N-homocysteinylation in rats. Hyperleptinemia was induced in adult rats by administration of leptin for 7 days (0.25 mg/kg twice daily s.c.). We found that serum Hcy-thiolactonase was lower in hyperleptinemic than in control animals (-41.0%, p<0.001). Leptin administration increased the level of N-linked Hcy in plasma proteins (+92.9%, p<0.01), but had no effect on plasma total Hcy. These effects were not reproduced by pair-feeding. We also found that the synthetic liver X receptor (LXR) agonist T0901317 (1 mg/kg/day) normalized Hcy-thiolactonase and protein N-homocysteinylation levels in leptin-treated rats. However, leptin-induced increase in plasma isoprostane levels (a marker of oxidative stress) was not normalized by T0901317. The NADPH oxidase inhibitor apocynin prevented leptin-induced increase in isoprostane levels but did not normalize Hcy-thiolactonase and protein N-homocysteinylation levels. These results suggest that the decreased capacity to metabolize Hcy-thiolactone and concomitant increase in protein N-homocysteinylation contribute to pro-atherogenic effect of chronic hyperleptinemia, independently of oxidative stress. LXR agonists normalize Hcy-thiolactonase levels and decrease protein N-homocysteinylation, especially under conditions associated with leptin excess such as metabolic syndrome.