Circulating leptin is associated with oxidized LDL in postmenopausal women
Introduction
Leptin is a plasma protein encoded by the ob gene, secreted by adipocytes and involved in the control of body weight [1]. Plasma concentrations of leptin are increased in human obesity and positively correlated to the body fat mass in lean and obese subjects [2]. In addition to long-term regulation of the body weight, hyperleptinemia has been considered as a component of the metabolic syndrome [3] and a role for leptin as a possible cause of vascular disease has been recently suggested [4], [5], [6], [7]. In this setting, it has been shown that leptin might exert an atherogenic effect through the generation of oxidative stress in endothelial cells [8].
Oxidized LDL (Ox-LDL) is a plaque specific lipoprotein that is directly involved in the initiation and progression of the atherosclerotic disease process [9]. Substantial evidence demonstrated that Ox-LDL are present in vivo, possibly reflecting the turnover of Ox-LDL formed in the vascular wall [10]. Elevated blood levels have been shown to be present in patients in all stages of coronary artery disease [11], [12], [13], [14]. Furthermore, Ox-LDL levels have been shown to be related to intima-media thickness and plaque occurrence in the carotid and femoral arteries of clinically healthy subjects [15].
Several risk factors of atherosclerosis have been also studied with respect to their possible effects on LDL oxidation [14]. In this setting, interestingly, a multivariate analysis showed that body mass index (BMI) was one of the most significant predictors of circulating levels Ox-LDL [14].
In the light of these observations, we hypothesised an in vivo relationship between plasma leptin and Ox-LDL levels. To explore this hypothesis, we evaluated the relationship between circulating Ox-LDL, leptin plasma levels and other risk factors of atherosclerosis, in sixty postmenopausal women at baseline and after a weight loss program carried out in a subgroup of subjects with BMI≥30. Our findings showed that Ox-LDL levels are associated with leptin levels independently of other risk factors and that decrease in leptin concentration induced by weight loss is a significant predictor of circulating changes in Ox-LDL.
Section snippets
Subjects and study protocol
Since previous studies demonstrated a gender and menopausal-dependent leptin plasma concentration [16], we decided to evaluate postmenopausal women referred to our vascular ambulatory service to screen for atherosclerosis risk factors. All patients had appropriate clinical and laboratory evaluations and were subjected to carotid ultrasonography for atherosclerosis assessment as previously described [17].
Body mass index (BMI) was used to distinguish between patients with normal weight (18–25 kg/m2
Results
The study group, whose characteristics are shown in Table 1, consisted of 60 postmenopausal women (age: 52±13 years). At the time of assessment, all of the study subjects were free of history of cardiovascular events (i.e. ischemic heart disease, cerebrovascular disease) and had no clinical evidence of atherosclerotic diseases. The mean intimal-media thickness (IMT) was 0.88±0.14 mm, no significant plaque was found at ultrasonographic assessment. All subjects were non-smokers, had normal fasting
Discussion
This study extends the observation of a relationship between circulating Ox-LDL and cardiovascular risk factors to circulating levels of leptin, a plasma protein recently suggested as a component of cardiovascular risk [3], [4], [5], [6], [7]. This association was present at univariate analysis and persisted after multivariate analysis including other cardiovascular risk factors and after changes induced by a weight loss program.
Several studies have tested circulating Ox-LDL in patients with
Acknowledgements
We thank Augusto Di Castelnuovo for the excellent assistance in statistical analysis. This work was supported by a grant from the Italian Ministry of Research to the Centre of Excellence on Aging of the University of Chieti.
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