Serum fetuin-A and retinol-binding protein 4 correlate with lipoprotein subfractions in obese and lean non-diabetic subjects

2021 ◽  
Vol 331 ◽  
pp. e201
Author(s):  
H. Lőrincz ◽  
I. Csige ◽  
M. Harangi ◽  
A. Szentpéteri ◽  
I. Seres ◽  
...  
Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 881
Author(s):  
Hajnalka Lőrincz ◽  
Imre Csige ◽  
Mariann Harangi ◽  
Anita Szentpéteri ◽  
Ildikó Seres ◽  
...  

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/m2) along with 32 gender and age-matched normal weight controls (BMI: 24.5 ± 2.5 kg/m2) 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 (p < 0.01 and p < 0.01, respectively) compared to controls and correlated with each other (r = 0.37; p < 0.001). Fetuin-A had positive correlations with HDL-C (r = 0.22; p = 0.02), apolipoprotein AI (apoAI) (r = 0.33; p < 0.001), very-low density lipoprotein (VLDL) subfraction (r = 0.18; p = 0.05), and large HDL subfraction levels (r = 0.3; p = 0.001) but did not show correlation with carbohydrate parameters in all subjects. RBP4 correlated positively with HDL-C (r = 0.2; p = 0.025), apoAI (r = 0.23; p = 0.01), VLDL subfraction (r = 0.37; p < 0.001), intermediate HDL subfraction (r = 0.23; p = 0.01), and small HDL subfraction (r = 0.21; p = 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.


2019 ◽  
Vol 8 (11) ◽  
pp. 1792 ◽  
Author(s):  
Hanna Wessel ◽  
Ali Saeed ◽  
Janette Heegsma ◽  
Margery A. Connelly ◽  
Klaas Nico Faber ◽  
...  

Background: Retinol binding protein 4 (RBP4) carries retinol in plasma, but is also considered an adipokine, as it is implicated in insulin resistance in mice. Plasma RBP4 correlates with total cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides, and may confer increased cardiovascular risk. However, controversy exists about circulating RPB4 levels in type 2 diabetes mellitus (T2DM) and obesity. Here, we analyzed the relationships of RBP4 and retinol with lipoprotein subfractions in subjects with and without T2DM. Methods: Fasting plasma RBP4 (enzyme-linked immunosorbent assay) and retinol (high performance liquid chromatography) were assayed in 41 T2DM subjects and 37 non-diabetic subjects. Lipoprotein subfractions (NMR spectroscopy) were measured in 36 T2DM subjects and 27 non-diabetic subjects. Physical interaction of RBP4 with lipoproteins was assessed by fast protein liquid chromatography (FPLC). Results: Plasma RBP4 and retinol were strongly correlated (r = 0.881, p < 0.001). RBP4, retinol and the RBP4/retinol ratio were not different between T2DM and non-diabetic subjects (all p > 0.12), and were unrelated to body mass index. Notably, RBP4 and retinol were elevated in subjects with metabolic syndrome (p < 0.05), which was attributable to an association with elevated triglycerides (p = 0.013). Large VLDL, total LDL and small LDL were increased in T2DM subjects (p = 0.035 to 0.003). Taking all subjects together, RBP4 correlated with total cholesterol, non-HDL cholesterol, LDL cholesterol, triglycerides and apolipoprotein B in univariate analysis (p < 0.001 for each). Age-, sex- and diabetes status-adjusted multivariable linear regression analysis revealed that RBP4 was independently associated with large VLDL (β = 0.444, p = 0.005) and small LDL particles (β = 0.539, p < 0.001). Its relationship with large VLDL remained after further adjustment for retinol. RBP4 did not co-elute with VLDL nor LDL particles in FPLC analyses. Conclusions: Plasma RBP4 levels are related to but do not physically interact with large VLDL and small LDL particles. Elevated RBP4 may contribute to a proatherogenic plasma lipoprotein profile.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Rene Quiroz ◽  
Kerrie P Nelson ◽  
John F Keaney ◽  
Emelia J Benjamin ◽  
Lisa M Sullivan ◽  
...  

Introduction: Recent investigations have highlighted the central role of mediators produced by adipose tissue in the pathogenesis of metabolic dysregulation. We evaluated a multimarker panel of 6 adipokines (adiponectin, leptin, leptin receptor, fetuin-A, adipocyte-fatty acid binding proteins, retinol binding protein-4 [RBP4]) and related them prospectively to the incidence of metabolic syndrome (MetS) and change in metabolic traits on follow-up in a community-based sample of younger adults. We hypothesized that these adipokines would be associated with incidence of MetS and with longitudinal tracking of its components. Methods and Results: We evaluated the adipokine panel measured in 2208 Framingham third generation cohort participants (55% women; mean age 40 years). On follow-up (mean 6 years), 253 individuals developed new-onset MetS. After adjustment for standard clinical risk factors, the multimarker adipokine panel was associated with incident MetS (P = 0.002). Using a backward elimination process, both RBP4 and fetuin-A were significantly associated with development of MetS (multivariable-adjusted OR per 1-SD increment log marker, 1.23 [P= 0.01] and 1.17 [P= 0.03], respectively). Using the group with both the RBP4 and fetuin-A under the median serving as the referent, individuals with levels of both RBP4 and fetuin-A above the median experienced an increased risk for developing MetS (multivariable adjusted OR = 1.7 [95% CI, 1.10 - 2.65], P = 0.01). In multivariable adjusted logistic regression models, both RBP4 and fetuin-A were significantly associated with an increase in systolic BP (P =0.004 and P = 0.045, respectively) and increased fasting glucose. In addition, RBP4 was significantly associated with longitudinal increase in diastolic BP (P = 0.007). Conclusions: Our findings, based on prospective follow-up of a large community-based sample of younger adults, suggest higher levels of RBP4 and fetuin-A are associated with incident MetS and may constitute potential future therapeutic targets.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Chuyao Jin ◽  
Lizi Lin ◽  
Na Han ◽  
Zhiling Zhao ◽  
Zheng Liu ◽  
...  

Abstract Background To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM). Methods Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM. Results The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0 μg/L vs 14.4 μg/L; P < 0.05). Plasma RBP4 concentrations in the first and second trimester were associated with fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) in the second trimester (all P < 0.001). With adjustment for diet, physical activity, and other risk factors for GDM, the risk of GDM increased with every 1-log μg/L increment of RBP4 levels, and the OR (95% CI) was 3.12 (1.08–9.04) for RBP4 in the first trimester and 3.38 (1.03–11.08) for RBP4 in the second trimester. Conclusions Plasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.


2021 ◽  
pp. 1-8
Author(s):  
Yuanhao Wu ◽  
Fan Wang ◽  
Tingting Wang ◽  
Yin Zheng ◽  
Li You ◽  
...  

<b><i>Background:</i></b> Arteriovenous fistula (AVF) is the most common vascular access for patients undergoing hemodialysis (HD). Neointimal hyperplasia (NIH) might be a potential mechanism of AVF dysfunction. Retinol-binding protein 4 (RBP4) may play an important role in the pathogenesis of NIH. The aim of this study was to investigate whether AVF dysfunction is associated with serum concentrations of RBP4 in HD subjects. <b><i>Methods:</i></b> A cohort of 65 Chinese patients undergoing maintenance HD was recruited between November 2017 and June 2019. The serum concentrations of RBP4 of each patient were measured with the ELISA method. Multivariate logistic regression was used to analyze data on demographics, biochemical parameters, and serum RBP4 level to predict AVF dysfunction events. The cutoff for serum RBP4 level was derived from the highest score obtained on the Youden index. Survival data were analyzed with the Cox proportional hazards regression analysis and Kaplan-Meier method. <b><i>Results:</i></b> Higher serum RBP4 level was observed in patients with AVF dysfunction compared to those without AVF dysfunction events (174.3 vs. 168.4 mg/L, <i>p</i> = 0.001). The prevalence of AVF dysfunction events was greatly higher among the high RBP4 group (37.5 vs. 4.88%, <i>p</i> = 0.001). In univariate analysis, serum RBP4 level was statistically significantly associated with the risk of AVF dysfunction (OR = 1.015, 95% CI 1.002–1.030, <i>p</i> = 0.030). In multivariate analysis, each 1.0 mg/L increase in RBP4 level was associated with a 1.023-fold-increased risk of AVF dysfunction (95% CI for OR: 1.002–1.045; <i>p</i> = 0.032). The Kaplan-Meier survival analysis indicated that the incidence of AVF dysfunction events in the high RBP4 group was significantly higher than that in the low-RBP4 group (<i>p</i> = 0.0007). Multivariate Cox regressions demonstrated that RBP4 was an independent risk factor for AVF dysfunction events in HD patients (HR = 1.015, 95% CI 1.001–1.028, <i>p</i> = 0.033). <b><i>Conclusions:</i></b> HD patients with higher serum RBP4 concentrations had a relevant higher incidence of arteriovenous dysfunction events. Serum RBP4 level was an independent risk factor for AVF dysfunction events in HD patients.


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