| Summary: | Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atherosclerosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have not been entirely investigated in morbid obese and lean non-diabetic subjects. Methods: One-hundred obese non-diabetic patients (body mass index, BMI: 42.5 ± 8.1 kg/m<sup>2</sup>) along with 32 gender and age-matched normal weight controls (BMI: 24.5 ± 2.5 kg/m<sup>2</sup>) were enrolled in our study. Serum fetuin-A and RBP4 were measured by ELISA. Lipoprotein subfractions were distributed by Lipoprint gelelectrophoresis. Results: Serum fetuin-A and RBP4 were unexpectedly lower in obese patients (<i>p</i> < 0.01 and <i>p</i> < 0.01, respectively) compared to controls and correlated with each other (r = 0.37; <i>p</i> < 0.001). Fetuin-A had positive correlations with HDL-C (r = 0.22; <i>p</i> = 0.02), apolipoprotein AI (apoAI) (r = 0.33; <i>p</i> < 0.001), very-low density lipoprotein (VLDL) subfraction (r = 0.18; <i>p</i> = 0.05), and large HDL subfraction levels (r = 0.3; <i>p</i> = 0.001) but did not show correlation with carbohydrate parameters in all subjects. RBP4 correlated positively with HDL-C (r = 0.2; <i>p</i> = 0.025), apoAI (r = 0.23; <i>p</i> = 0.01), VLDL subfraction (r = 0.37; <i>p</i> < 0.001), intermediate HDL subfraction (r = 0.23; <i>p</i> = 0.01), and small HDL subfraction (r = 0.21; <i>p</i> = 0.02) concentrations, as well as C-peptide levels in overall participants. Backward stepwise multiple regression analysis showed that serum fetuin-A concentration is best predicted by RBP4 and large HDL subfraction. In model 2, VLDL subfraction was the independent predictor of serum RBP4 level. Conclusions: Our data may indicate a potential role of fetuin-A and RBP4 in impaired lipoprotein metabolism associated with obesity.
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