Paper Report for: Beltowski_2010_J.Endocrinol_204_191
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Title: Modulation of paraoxonase 1 and protein N-homocysteinylation by leptin and the synthetic liver X receptor agonist T0901317 in the rat Beltowski J, Wojcicka G, Jakubowski H Ref: J Endocrinol, 204:191, 2010 : PubMed
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 that has the ability to hydrolyze Hcy-thiolactone and minimizes protein N-homocysteinylation. Here we examined the 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 per 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 excess leptin such as metabolic syndrome.
        
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Beltowski J, Wojcicka G, Jakubowski H (2010) Modulation of paraoxonase 1 and protein N-homocysteinylation by leptin and the synthetic liver X receptor agonist T0901317 in the rat J Endocrinol204: 191-8
Beltowski J, Wojcicka G, Jakubowski H (2010) J Endocrinol204: 191-8