Serum Concentrations Of Retinol-binding Protein 4 Research Articles

Does Retinol-Binding Protein 4 (holo- and apo-RBP4) Increase or Remain Constant in Sera from Patients with Hypothyroidism?

Retinol-binding protein 4 (RBP4) is a retinol transporter in the blood plasma. Many diseases alter the plasma or serum levels of RBP4. Since serum RBP4 concentrations have been reported to decrease in hyperthyroidism, this study investigated whether serum RBP4 concentrations increased or remained constant in hypothyroidism. In sera from patients with hypothyroidism (n=71), hyperthyroidism (n=30), and healthy subjects (n=20), serum concentrations of RBP4 (sum of holo- and apo-RBP4), retinol, albumin, creatinine, and related constituents were measured, and RBP4/retinol molar ratio (as an index of apo-RBP4) and estimated glomerular filtration rate (eGFR) were calculated. The results showed that serum RBP4 concentrations tended to increase with decreasing free thyroxine concentrations, but there were no significant differences among patients with hypothyroidism, hyperthyroidism, and healthy subjects. When patients with hypothyroidism were subdivided by serum RBP4 level using 2.1 μmol/L cut-off value, patients with >2.1 μmol/L were revealed to be patients with older age having lower tri-iodothyronine, higher holo-RBP4, higher apo-RBP4, higher retinol, higher RBP4/retinol molar ratio, and lower eGFR than those in patients with <2.1 μmol/L. Multiple regression analysis showed significant associations between serum RBP4 levels and explanatory variables (retinol and eGFR). Although serum levels of RBP4 prior to the onset of renal dysfunction may affect the present concentrations, we conclude that the increase of serum RBP4 (both holo- and apo-RBP4) in patients with hypothyroidism was attributed to the decline in eGFR. In contrast, serum RBP4 concentration remained constant without renal dysfunction.

Association of Retinol-Binding Protein 4 with Arteriovenous Fistula Dysfunction in Hemodialysis Patients

Background: 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. Methods: 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. Results: 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, p = 0.001). The prevalence of AVF dysfunction events was greatly higher among the high RBP4 group (37.5 vs. 4.88%, p = 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, p = 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; p = 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 (p = 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, p = 0.033). Conclusions: 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.

Are adipokines associated with gestational diabetes mellitus?

To investigate the association of maternal serum levels of chemerin, retinol binding protein-4 (RBP-4), and visfatin with gestational diabetes mellitus (GDM). 158 pregnant women were screened between 24 and 28 weeks of gestation. They were divided into two groups: GDM group (n=76) and control group (n=82). Maternal serum concentrations of chemerin, RBP-4, visfatin, insulin, and homeostasis model assessment-insulin resistance (HOMA-IR) were assessed. There were no differences in age and gestational age between the GDM group and the control group (p=0.058 and p=0.820, respectively). Body mass index (BMI) at 24 to 28 weeks of gestation was higher in the GDM group (p<0.001). The serum concentrations of RBP-4, chemerin, and visfatin did not demonstrate significant differences between the GDM and control groups (p=0.871, p=0.100, and p=0.886, respectively). Significant differences in serum level of insulin and HOMA-IR were found between the GDM and control groups (14.94 vs 9.87, p<0.001 and 3.73 vs 1.77, p<0.001, respectively). Correlation analyses of chemerin, RBP-4, visfatin, insulin, and HOMA-IR in both groups revealed a weak degree of positive correlation between RBP-4 and chemerin (Spearman r=0.251, p=0.026) and a strong positive correlation between maternal insulin and HOMA (Spearman r=0.868, p<0.001). No differences were found in serum chemerin, RBP-4, and visfatin between pregnant women with GDM and healthy pregnant women. Further prospective studies will be essential to elucidate the contribution of adipokines to GDM and the positive correlation between maternal RBP-4 and chemerin.

Circulating levels of lipocalin-2 and retinol-binding protein-4 are increased in psoriatic patients and correlated with baseline PASI

Psoriasis has been related to metabolic syndrome (MS). Adipocytokines produced by white adipose tissue may be involved in the pathogenesis of psoriasis and its association with MS. Our objectives were to characterize the profile of a number of different inflammatory and atherogenic markers, vitamins, adipokines and cytokines and their potential involvement in MS in patients with moderate-to-severe psoriasis without joint involvement compared to anthropometrically matched controls, and to evaluate correlation with severity of the skin disease and changes after narrow-band UVB (NB-UVB) phototherapy. We designed a prospective cross-sectional study. Baseline waist circumference, body fat composition, lipid, carbohydrate and calcium metabolism profile, inflammation markers, homocysteine and vitamins D, B6, B12 and folic acid, leptin, resistin, omentin, lipocalin-2, adipocyte fatty acid-binding protein, retinol-binding protein-4 (RBP-4), interleukin-6, soluble tumour necrosis factor receptor 1 (sTNFR1) and interleukin-17 of 50 psoriasis patients and 50 gender, age and body mass index-matched controls were recorded, then evaluated after NB-UVB in the patients. The patients had higher baseline serum concentrations of leptin, RBP-4, lipocalin-2 and sTNFR1. Baseline psoriasis area and severity index correlated with serum concentrations of RBP-4 and lipocalin-2 only. Principal components analysis disclosed a component including vitamins B12, B6, folic acid, calcidiol and HDL-cholesterol that was only present in healthy controls and opposed to a cluster of variables which promote MS. This component was absent in the patients. Our results point to lipocalin-2 and RBP-4 as relevant mediators of the trend towards MS in psoriatic patients.

Serum retinol binding protein-4 and neutrophil gelatinase-associated lipocalin are interrelated in pancreatic cancer patients

Objectives. Pancreatic cancer has an extremely dismal clinical course and high fatality rate. Knowing that, adipokines could regulate insulin resistance, inflammation, immunity and carcinogenesis. Accordingly, an understanding of adipokines in relation to pancreatic cancer could be useful to improve disease outcome. We aimed to determine serum retinol binding protein-4 (RBP-4) and neutophil gelatinase-associated lipocalin (NGAL) levels in pancreatic cancer patients. Moreover, we assessed their association with tumor severity and with each other. Methods. A total of 23 pancreatic cancer patients and 20 healthy controls were enrolled. Fifteen of the pancreatic cancer patients underwent Whipple resection and were examined before and after operation. Serum glucose, insulin, lipid profile, CA19-9, RBP-4 and NGAL were estimated by ELISA. Results. Significant elevation in serum concentrations of RBP-4 (64.4 ± 5.6 ng/ml) and NGAL (142(80–235) ng/ml) at p < 0.001 was found in pancreatic cancer patients. Both RBP-4 and NGAL were significantly lower after operation than before operation. Moreover, NGAL was elevated in advanced pathological T stage. Interestingly, RBP-4 and NGAL levels were positively correlated (r = 0.484, p = 0.05) and they are associated with some of the lipid profile parameters. Conclusions. Elevated serum RBP-4 and NGAL are associated with pancreatic cancer. They were positively interrelated; highlighting the possible interplay between them in pancreatic cancer.

Elevated serum retinol-binding protein 4 concentrations are associated with chronic kidney disease but not with the higher carotid intima-media thickness in type 2 diabetic subjects

To examine the association of serum retinol-binding protein 4 (RBP4) concentrations with carotid intima-media thickness (CIMT) in type 2 diabetic subjects with chronic kidney disease (CKD). A total of 239 type 2 diabetic patients (64 ± 13 years, 154 males) were divided into two groups: one with CKD, defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m(2) (n = 86), and one without (n = 153). We recorded clinical and biochemical data as well as CIMT. The patients with CKD were older, had had diabetes mellitus longer, and had higher incidence of hypertension, dyslipidemia and microalbuminuria than those without. They also had higher serum concentrations of RBP4 (44.8 ± 6.4 vs 39.5 ± 4.9 µg/mL, p < 0.001), higher mean CIMT (0.75 ± 0.16 vs 0.69 ± 0.14 mm, p = 0.0070), and higher incidence of carotid plaques (27.9 vs 11.8 %, p = 0.002). The RBP4 were negatively correlated with eGFR (r = -0.514, p < 0.001). However, the RBP4 were not correlated with mean CIMT (r = 0.065, p = 0.318). Moreover, when dividing the patients into two groups by the mean CIMT, those with mean CIMT above 0.71 mm did not have different RBP4 concentrations compared with those below (41.5 ± 5.7 vs 41.3 ± 6.3 µg/mL, p = 0.856). In conclusion, we observed an elevation of serum RBP4 concentrations and CIMT levels in type 2 diabetic subjects with CKD. However, the elevated RBP4 were not associated with the higher CIMT among these patients.

Depot-specific expression of retinol-binding protein 4 in human adipose tissue and their relationship with obesity and insulin resistance

To explore the depot-specific mRNA and protein expression of retinol-binding protein 4 (RBP4) in human subcutaneous and omental adipose tissue and investigate their relationship with the serum RBP4 levels, obesity and insulin resistance. A total of 41 subjects with normal glucose regulation were recruited. Among them, there were 29 cases with normal body mass index (BMI) and 12 cases with BMI ≥ 24 kg/m(2). All were prepared to undergone a selective abdominal surgery. The levels of serum RBP4 and fasting insulin (FINS) were measured by ELISA (enzyme-linked immunosorbent assay) and chemiluminescence ELISA kit respectively. Fasting plasma glucose (FPG) was tested by glucose oxidase and the home model insulin resistance index (HOMA-IR) calculated. Real-time PCR (RT-PCR) and Western blot were employed to assess the relative mRNA and protein expression of RBP4 in subcutaneous and omental adipose tissues. The mRNA and protein expression of RBP4 from different fat depots were compared and their correlations with BMI, the serum RBP4 concentrations and HOMA-IR analyzed. (1) The serum concentrations of RBP4, FINS and HOMA-IR were significantly higher in overweight and obesity group than those in the normal BMI group [RBP4: (39.61 ± 1.57) mg/L vs (33.40 ± 1.28) mg/L, P < 0.01; FINS: (8.82 ± 3.79) mU/L vs (6.43 ± 4.38) mU/L, P < 0.05; HOMA-IR: 1.91 ± 0.85 vs 1.36 ± 0.72, P < 0.05]. (2) The expression levels of RBP4 mRNA and protein were significantly higher in omental adipose tissues than those in subcutaneous adipose tissue [mRNA: (5.88 ± 2.37) vs (2.07 ± 1.66), P < 0.01; protein: (0.76 ± 0.18 vs 0.15 ± 0.07, P < 0.05] and these depots difference in both groups (P < 0.05). Moreover, the overweight patients had the higher expression levels of RBP4 mRNA and protein in omental adipose tissue than normal BMI group (mRNA: 7.52 ± 0.58 vs 4.37 ± 0.45, P < 0.01; protein: 0.92 ± 0.23 vs 0.57 ± 0.13, P < 0.05). (3) The expressions of both RBP4 mRNA and protein in the omental adipose tissue were positively correlated with BMI, waist circumstance, serum concentrations of RBP4, FINS and HOMA-IR. The expression of was negatively correlated with HOMA-IR (r = -0.635, P < 0.05) in subcutaneous adipose tissue. No correlations were found between the expressions of RBP4 mRNA and protein in subcutaneous adipose tissue with BMI, waist circumstance, serum RBP4 and FINS concentrations. There is depot-specific expression of RBP4 in human subcutaneous and omental adipose tissues. A high expression of RBP4 in omental adipose tissue and an elevated level of serum RBP4 may contribute to the pathogenesis of obesity and IR.

Correlation of retinol binding protein 4 expression in maternal serum and subcutaneous adipose tissue with insulin resistance in gestational diabetes mellitus.

To investigate the expression of retinol binding protein 4 (RBP-4) in maternal serum and subcutaneous adipose tissue and its relationship with insulin resistance (IR) in gestational diabetes mellitus (GDM). From May 2008 to April 2009, 62 pregnant women who underwent elective cesarean section in the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College, were recruited, including 32 with GDM (GDM group) and 30 with normal glucose tolerance test (control group). Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum concentrations of RBP-4 and radio immunoassay to measure the serum levels of fasting insulin (FINS). Fasting plasma glucose (FPG) was tested by glucose oxidase, and the Home model insulin resistance index (HOMA-IR) was calculated. Reverse transcription PCR (RT-PCR) and Western blot were applied to investigate the expression of RBP-4 mRNA and protein in subcutaneous adipose tissue. The correlations between the expression of RBP-4 mRNA and protein in subcutaneous adipose tissue and the serum RBP-4 concentrations and HOMA-IR were analyzed. (1) The serum concentrations of RBP-4, FINS, FPG, HOMA-IR in GDM group were significantly higher compared with the control group [(27.0 +/- 1.2) mg/L vs. (19.4 +/- 1.8) mg/L, (12.1 +/- 1.4) mU/L vs. (8.3 +/- 0.8) mU/L, (5.3 +/- 0.9) mmol/L vs. (4.1 +/- 0.6) mmol/L, 2.5 +/- 0.2 vs. 1.5 +/- 0.1, P < 0.05, respectively]. (2) The expression of RBP-4 mRNA and protein in subcutaneous adipose tissue in the GDM group were significantly higher than that of the control group (0.76 +/- 0.12 vs. 0.53 +/- 0.06, 0.74 +/- 0.09 vs 0.54 +/- 0.06, P < 0.05). (3) In the GDM group, the expression of both RBP-4 mRNA and protein in the subcutaneous adipose tissue were positively correlated with HOMA-IR (r = 0.575 and 0.851, P < 0.05). The serum concentration of RBP-4 were also positively correlated with HOMA-I (r = 0.635, P < 0.05). No correlations was found between the expressions of RBP-4 mRNA and protein in subcutaneous adipose tissue with the serume RBP-4 concentrations. High expression of RBP-4 mRNA in subcutaneous adipose tissue and the elevation of serum RBP-4 levels in GDM women may contribute to IR.

Serum Retinol-Binding Protein 4 Is Reduced after Weight Loss in Morbidly Obese Subjects

Administration of retinol-binding protein 4 (RBP-4) impairs insulin sensitivity in animals, and elevated serum concentrations have been associated with insulin resistance in humans. We have studied whether weight loss influences RBP-4. Fasting serum concentrations of RBP-4 were measured before and 6 months after gastric banding surgery in 33 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls. To characterize the association of weight loss with central and peripheral appetite regulation, the signaling protein agouti-related protein (AGRP), the orexigenic hormone ghrelin, and its recently identified antagonist obestatin were determined. At baseline, RBP-4 levels were markedly higher in obese than in lean subjects (2.7 +/- 0.5 vs. 0.9 +/- 0.5 microg/ml; P < 0.001). In contrast, AGRP and obestatin were lower in obese subjects compared with lean controls (all P < 0.001). Six months after gastric banding, BMI was reduced to 40 +/- 5 kg/m(2), RBP-4 was reduced to 2.0 +/- 0.7 microg/ml, AGRP increased from 1.8 +/- 1.1 to 3.4 +/- 1.1 ng/ml, ghrelin increased from 93 +/- 58 to 131 +/- 70 pg/ml, and obestatin increased from 131 +/- 52 to 173 +/- 35 pg/ml (all P < 0.05). Individual changes of RBP-4 were associated with changes of BMI (r = 0.72), the homeostasis model assessment insulin resistance-index (r = 0.53), and total cholesterol (r = 0.42, for all P < 0.05). Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. This is accompanied by favorable changes in appetite-regulating hormones, which might support the sustained weight loss after obesity surgery.