Relationship of endogenous hyperleptinemia to serum paraoxonase 1, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase in obese individuals.
Altered activities of high-density lipoprotein (HDL)-associated antioxidant enzyme paraoxonase 1 (PON1) and lipid transfer proteins, for example, cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT), participating in lipoprotein remodeling seem to play important roles in obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum leptin levels have been demonstrated. However, the relationship of leptin with CETP and LCAT in humans is less clear. Our aims were to investigate whether the elevated leptin level is (a) an independent predictor of low PON1 and (b) associated with alterations of CETP and LCAT activities. Seventy-four white subjects forming 3 age- and sex-matched groups were included into the study (groups 1 and 2: nondiabetic obese patients, n = 25 with body mass index [BMI] 28-39.9 kg/m2 and n = 25 with BMI >or=40 kg/m2, respectively; and group 3: 24 healthy, normal-weight control subjects). Paraoxonase 1 correlated inversely with BMI (r = -0.39, P < .01), waist circumferences (r = -0.42, P < .001), and leptin concentrations (r = -0.38, P < .001). However, in a multiple regression model, neither these variables nor others, for example, age, sex, blood pressure, insulin resistance (in homeostasis model assessment of insulin resistance [HOMA-IR]), HDL cholesterol, low-density lipoprotein cholesterol, or lipid peroxidation (measured as thiobarbituric acid reactive substances), proved to be independent predictors of PON1. Lecithin cholesterol acyltransferase correlated negatively with BMI (r = -0.40, P < .01), waist circumferences (r = -0.42, P < .001), and leptin levels (r = -0.40, P < .01). During multiple regression analyses, BMI was an independent predictor of LCAT after adjustments for age, sex, HOMA-IR, and HDL cholesterol. However, this was replaced by leptin and HOMA-IR when leptin was also included into the model. The CETP activities correlated with HOMA-IR (r = 0.33, P < .01), thiobarbituric acid reactive substances (r = 0.45, P < .001), and leptin (r = 0.36, P < .01) levels in univariate but not in multivariate models. Elevated leptin level is an independent predictor of low LCAT, but not PON1, activity. In a population with a wide range of BMI, LCAT correlates inversely with obesity and CETP directly with insulin resistance.
Bajnok
Laszlo
L
1st Department of Medicine, School of Medicine, University of Pécs, Pécs, Hungary H-7624 Pécs, Hungary. laszlo.bajnok@aok.pte.hu
Seres
Ildiko
I
Varga
Zsuzsa
Z
Jeges
Sara
S
Peti
Attila
A
Karanyi
Zsolt
Z
Juhasz
Attila
A
Csongradi
Eva
E
Mezosi
Emese
E
Nagy
Endre V
EV
Paragh
Gyorgy
G
D000328:Adult; D043303:Aryldialkylphosphatase / Q000097:blood*; D015992:Body Mass Index; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*
D053480:Cholesterol Ester Transfer Proteins; D020738:Leptin; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D043303:Aryldialkylphosphatase