Retinol-binding Protein Concentrations Research Articles

Elevated Plasma Retinol-Binding Protein 4 Is Associated with Increased Risk of Type 2 Diabetes in Middle-Aged and Elderly Chinese Adults1–3

The association between circulating retinol-binding protein 4 (RBP4) and risk of type 2 diabetes has been inconsistent in cross-sectional studies, but prospective evidence is limited. We aimed to investigate whether plasma RBP4 is associated with future development of type 2 diabetes and whether the association could be explained by iron or other risk factors. A total of 2091 Chinese adults aged 50–70 y were followed up for 6 y. Baseline dietary intakes and fasting plasma RBP4, ferritin, adiponectin, C-reactive protein (CRP), γ-glutamyltransferase, creatinine, and erythrocyte fatty acids were determined. Self-reported doctor-diagnosed diabetes, or usage of antidiabetic agents, or fasting plasma glucose concentration at the follow-up visit ≥7.0 mmol/L was defined as an incident diabetes case. Plasma RBP4 concentration was significantly associated with dietary heme iron intake, plasma ferritin concentration, and other established risk factors. After multivariate adjustment for demographic and lifestyle variables, relative risk (RR) for type 2 diabetes when the extreme quartiles of RBP4 were compared was 1.75 (95% CI: 1.30, 2.37; P-trend < 0.001). This association remained significant when the extreme quartiles were compared (RR = 1.48; 95% CI: 1.06, 2.05; P-trend = 0.036) after further controlling for ferritin and dietary factors, as well as other risk factors, including body mass index, adiponectin, CRP, lipids, liver and kidney function, insulin resistance, and hypertension. A threshold effect of RBP4 concentrations on incident diabetes was suggested by restricted quadratic spline analysis (P = 0.026 for nonlinearity). Our study indicates that plasma RBP4 is independently associated with the 6-y risk of developing type 2 diabetes.

Associations between tissue retinol binding protein‐4, visfatin and vaspin protein concentrations and blood triglyceride and cholesterol levels in morbidly obese subjects (133.3)

Background: Obesity is associated with insulin resistance, diabetes, and cardiovascular diseases. Retinol binding protein‐4 (RBP‐4), visfatin and vaspin are known to have some effect on insulin resistance although their effects on cardiovascular diseases are not clear. Our research focuses on tissue secretions of RBP‐4, visfatin and vaspin proteins and their relationships to blood lipids.Methods: Thirty eight morbidly obese (BMI 蠅40) subjects had the subcutaneous, omental, and mesenteric adipose, liver and muscle tissue samples taken at the time of Roux‐n‐Y surgeries. Total proteins were extracted with RIPA solution and measured with ELISA kits (Adipogen, Korea). Blood triglycerides and cholesterols levels were measured using standard methods. Results were analyzed using Pearson correlation with p &lt;0.05 being significant.Results: Omental adipose tissue visfatin protein concentrations were positively correlated with blood total cholesterol levels (r = 0.382, p = 0.018). Muscle tissue visfatin protein concentrations were negatively correlated with blood HDL cholesterol levels (r = ‐0.384, p = 0.017). Omental adipose tissue RBP‐4 protein concentrations were positively correlated with blood triglyceride levels (r = 0.404, p = 0.012). Mesenteric adipose tissue vaspin concentrations were positively correlated with blood total cholesterol levels (r = 0.429, p = 0.007).Conclusions: Our findings indicate that tissue RBP‐4, visfatin and vaspin protein concentrations might have effects related to dyslipidemia during obesity.

The effect of acute exercise on circulating serum retinol binding protein 4 in seniors with and without impaired glucose tolerance (863.4)

Retinol binding protein 4 (RBP4) is an adipokine that contributes to insulin resistance and impaired glucose tolerance. There are no published reports concerning the influence of acute exercise on circulating RBP4. We sought to characterize this response in (1) healthy, normoglycemic males (CON; 23±4 y, BMI 22.3±9.4), (2) seniors with normal fasting glucose and glucose tolerance (S‐NGT; 70±5 y, BMI 24.2±6.5), and (3) seniors with impaired glucose tolerance (S‐IGT; 73±8 y, BMI 26.4±5.3; n=7 per group). Glucose tolerance was based on a 75 g oral glucose tolerance test wherein 2 h glucose values (mg/dL) were: 97±21 (CON), 106±24 (S‐NGT), and 159±13 (S‐IGT; p&lt;0.05 vs. CON and S‐NGT). 48 h after determining VO2max (ml/kg/min) in CON (56±10, p&lt;0.05 vs. S‐NGT and S‐IGT), S‐NGT (33±8), and S‐IGT (29±8) subjects, participants completed 20‐min of cycling at 85% VO2max. RBP4 was assessed (ELISA) in venous samples obtained before exercise and 50‐min and 24 h post exercise. Pre‐exercise RBP4 concentrations (ug/mL) were greater (p&lt;0.05) in S‐IGT (76±23) vs. S‐NGT (61±7) or CON (44±7) subjects. Values obtained at 50‐min and 24 h post exercise showed further increases after exercise (p&lt;0.05) in the S‐IGT (99±23 and 77±25, respectively) vs. both S‐NGT (56±7 and 39±9) and CON subjects (40±7 and 47±21). These data indicate that in senior subjects with IGT, circulating RBP4 is elevated before exercise, with persistent elevation in recovery (50‐min and 24 h) from exercise. Ongoing studies will determine whether skeletal muscle RBP4 regulates insulin‐glucose homeostasis.

Retinol binding protein 4 promotes hyperinsulinism-induced proliferation of rat aortic smooth muscle cells

Recent studies have suggested that retinol binding protein 4 (RBP4), an adipocytokine related to insulin resistance (IR), may play an important role in the development of atherosclerosis and cardiovascular diseases (CVD). Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is one of the most common causes of atherosclerosis. Hyperinsulinism promotes proliferation of VSMCs through the MAPK pathway. However, whether RBP4 is involved in insulin-induced proliferation of VSMCs leading to atherosclerosis remains unclear. In the present study, we evaluated the role of RBP4 and the potential relevance of signaling pathways in this process. Different concentrations of RBP4 (1 and 4 μg/ml) were added to rat aortic smooth muscle cells (RASMCs) during insulin-induced proliferation. The levels of cell growth signaling pathway proteins ERK1/2, p-ERK1/2, JAK2, p-JAK2, STAT3 and p-STAT3 were assessed by western blotting in order to identify the pathway(s) that are activated during insulin-induced proliferation. The specific inhibitors of ERK1/2 (PD98059) and JAK2 (AG490) were used to confirm our findings. Insulin induced proliferation of RASMCs in a concentration- and time-dependent manner, and increased the expression of ERK1/2, p-ERK1/2, JAK2, p-JAK2, STAT3 and p-STAT3 in a time-dependent manner. RBP4 enhanced insulin-induced proliferation of RASMCs and expression of p-ERK1/2 and p-JAK2. RBP4-induced proliferation of RASMCs was reduced by the ERK1/2 inhibitor, while it was unaffected by the JAK2 inhibitor. These results suggest that RBP4 mediates VSMC proliferation induced by insulin via activation of the MAPK pathway, and highlight RBP4 as a modulator of atherosclerosis in hyperinsulinemia, therby enhancing our understanding on a number of unexpected aspects of CVD.

Randomized Controlled Trial of a Protein Substitute with Prolonged Release on the Protein Status of Children with Phenylketonuria

Objective: To examine whether a phenylalanine-free protein substitute with prolonged release may be beneficial to the protein status of children with phenylketonuria (PKU) compared to conventional substitutes. Methods: Sixty children with PKU, 7 to 16 years of age, were randomly allocated to receive either a prolonged-release (test) or the current conventional protein substitute for 30 days. Subjects were additionally sex and age matched with 60 subjects with mild hyperphenylalaninemia and 60 unaffected subjects. The protein status in children with PKU was assessed by albumin, transthyretin, and retinol-binding protein (RBP), and changes throughout the trial period were the primary outcome measures. Results: Children with PKU did not differ in anthropometry from children with mild hyperphenylalaninemia or unaffected children but they ingested lower amounts of proteins (p < 0.01). No differences occurred throughout the trial between or within children with PKU who received the test or conventional substitute for macronutrient intake. Albumin and RBP concentrations were within the age-specific reference range for all children. The rate of protein insufficiency (transthyretin concentration less than 20 mg/dL) did not differ statistically between children receiving test or conventional substitute (recruitment 51.8% vs 53.6%; end of the trial 44.4% vs 50.0%) but mean transthyretin recovered over 20 mg/dL in children who received the test substitute, increasing from 19.1 to 20.7 mg/dL (mean change, 1.6 mg/dL; 95% confidence interval 0.4 to 2.8 mg/dL). In children receiving conventional substitute mean transthyretin changed from 19.0 to 19.2 mg/dL (0.2; −0.2 to 0.6) mg/dL. Conclusions: Protein substitutes with prolonged release might be beneficial to protein status in children with phenylketonuria.

Effect of endurance training on retinol-binding protein4 gene expression and its protein level in adipose tissue and the liver in diabetic rats induced by a high-fat diet and streptozotocin.

The present study was designed to investigate from which tissues the decrease in retinol-binding protein 4 (RBP4) expression could contribute to the improvement of serum RBP4 and insulin resistance (IR) after endurance training. Male 7-week-old Wistar rats were randomly assigned into four groups including control (C), trained (T), diabetic control (DC) and trained diabetic (TD). At 8weeks-of-age, diabetes was induced by a high-fat diet and intraperitoneal injection of low-dose streptozotocin (STZ; 35mg/kg). Rats in the T and TD groups carried out a 7-week exercise program on a motorized treadmill (15-20m/min for 20min/day for 5weeks), whereas the C and DC remained sedentary in their cages. Tissues gene expression and protein levels of RBP4 were assessed by using real-time polymerase chain reaction and western blot, respectively, while serum RBP4 was measured using an enzyme-linked immunosorbent assay kit. Exercise significantly improved IR and reduced serum concentration of RBP4 in the TD group. This reduction of serum RBP4 was accompanied by decreased RBP4 protein expression in visceral fat tissue. In contrast, exercise had no significant effect on RBP4 expression in liver and subcutaneous fat tissue in the TD group. Exercise also significantly decreased RBP4 gene expression in visceral fat tissue and muscle, whereas the effect of exercise on liver RBP4 messenger ribonucleic acid expression was not significant. The present study showed that the mechanism for RBP4 reducing the effect of endurance training could involve decreased RBP4 messenger ribonucleic acid expression and its protein level in adipose tissue in STZ-induced diabetic rats.

Novel biomarkers for prediction of poor treatment response in heart failure to guide therapy

BackgroundHeart failure is a complex clinical syndrome that occurs at the end stage of heart disease. It is a major health problem in western countries with an overall population prevalence of 2–3% which rises sharply to 10–20% at 75 years of age. Despite advances in therapy for heart failure, improvment of clinical outcomes remains a challenge for physicians: half of patients die within 4 years of diagnosis and 40% of patients, who have been admitted to hospital are dead or re-admitted to hospital within 1 year. The aim of this study was to find plasma proteins that predict differences in clinical response from standard therapy in patients with heart failure. MethodsPatients with heart failure who met inclusion and exclusion criteria were recruited. Uptitration of angiotensin-converting-enzyme-inhibitors and β blockers was done over 6 months. Patients were followed up for clinical events such as death and admission to hospital for heart failure within the next 24 months. We compared plasma proteins in 50 patients who responded to standard treatment (responders) with 50 patients who died or were re-admitted to hospital (non-responders). Plasma samples were pooled and depleted of 14 high abundance proteins and then reduced and alkylated, before digestion with trypsin to peptides. Peptides were analysed on two-dimensional liquid chromatography coupled to a tandem mass spectrometry in high definition mode which used a high pH reverse phase liquid chromatography in the first step before separation with conventional low pH reverse phase columns in the second step. Findings434 proteins were identified in the plasma of patients with heart failure. 137 proteins in both responders and non-responders were significantly overexpressed or underexpressed (p<0·05), with 97 upregulated and 40 downregulated. Several of these proteins have the potential to become novel biomarkers for prediction of treatment response. They can be classified according to five pathobiological processes in heart failure: (1) neurohormones—hepatocyte growth factor like protein and insulin like growth factor II; (2) vascular system—intercellular adhesion molecule 2, sex hormone binding globulin, and prostaglandin H2 D isomerase; (3) inflammation—C-reactive protein, and mannose binding protein C; (4) matrix and cellular remodelling—retinol binding protein 4; and (5) cardiorenal system—cystatin C. InterpretationThe discovery of novel biomarkers in this study will not only help to understand the pathophysiology of heart failure better, but also lead to the development of a more personalised approach in predicting treatment response to guide medical therapy. For example, in patients with heart failure who have abnormally increased concentrations of retinol-binding protein 4, a marker for matrix and cellular remodelling, a drug for reducing collagen deposition could be useful. In this way, unnecessary treatment in non-responders could be avoided (with implications for cost and adverse effects) and novel therapeutic targets could be identified for design of therapies to improve outcomes. FundingEuropean Union FP7 Project.

Breast Milk Retinol and Plasma Retinol-Binding Protein Concentrations Provide Similar Estimates of Vitamin A Deficiency Prevalence and Identify Similar Risk Groups among Women in Cameroon but Breast Milk Retinol Underestimates the Prevalence of Deficiency among Young Children1–3

Breast milk vitamin A (BMVA) has been proposed as an indicator of population vitamin A status but has rarely been applied in large-scale surveys or compared with conventional vitamin A biomarkers. We assessed the prevalence of, and risk factors for, low BMVA and its relation to vitamin A intake, plasma retinol-binding protein (pRBP), and markers of inflammation in a national survey in Cameroon. We randomly selected 30 clusters in each of 3 strata (South, North, and Cities). Casual milk samples were collected from approximately 5 women per cluster (n = 440). pRBP, plasma C-reactive protein (pCRP), plasma α1-acid glycoprotein (pAGP), and 24-h vitamin A intake were assessed in 10 women aged 15–49 y and 10 children aged 12–59 mo per cluster, including a subset of lactating women (n = 253). Low BMVA was infrequent: 7.2% (95% CI: 4.7, 9.8) of values were <1.05 μmol/L, and 9.3% (95% CI: 5.8, 12.7) were <8 μg/g fat, consistent with the low prevalence of pRBP <0.78 μmol/L among women (< 5%) but lower than the prevalence of pRBP <0.83 μmol/L among children (35%). Risk factors for both low BMVA and pRBP included living in the North and low maternal education. BMVA was positively associated with inflammation-adjusted pRBP among women in the lowest vitamin A intake tertile [<115 μg retinol activity equivalents (RAEs)/d, P < 0.01] but not in the highest tertile (>644 μg RAEs/d, P > 0.4). Controlling for milk fat, BMVA was negatively associated with pCRP (P < 0.02) but not pAGP (P > 0.5). BMVA and pRBP provide similar estimates of vitamin A deficiency prevalence and identify the same risk groups among women in Cameroon, but BMVA underestimates the prevalence of vitamin A deficiency among young children.

An ITO Based Disposable Biosensor for Ultrasensitive Analysis of Retinol Binding Protein

AbstractA highly sensitive electrochemical biosensor based on anti‐RBP biorecognition capable to analyze concentrations of retinol binding protein (RBP) was developed. The construction of the biosensor interfaces was carefully characterized by techniques such as electrochemistry, EIS, and scanning electron microscopy. In order to characterize impedance data, Kramers‐Kronig Transform was performed on the experimental impedance data. Besides, for an immunosensor system the Single Frequency Impedance technique was firstly used for the characterization of the interaction between RBP and anti‐RBP. Finally, artificial serum samples spiked with RBP were analyzed by the proposed ITO based immunosensor to investigate the usefulness of the biosensor for early biomarker diagnosis.

Serum levels of vascular endothelial growth factor in patients with gastrointestinal cancers and correlation with malnutrition, immunosuppression involving MDSC, and systemic inflammation.

514 Background: Vascular endothelial growth factor (VEGF) reportedly plays an important role in the progression of malignant neoplasms, and have been reported to induce myeloid-derived suppressor cells (MDSC) that appears in cancer and inflammation. Methods: Blood samples were collected from 57 patients, including 8 with esophageal cancer, 20 with gastric cancer, 29 with colorectal cancer, and from 18 healthy volunteers. We measured serum concentrations of VEGF and analyzed correlations with nutritional damage, immune suppression and systemic inflammation. As markers of immune function, IL-12 production of PBMC and MDSC (CD 11b+, CD14-, CD33+) were measured. Serum concentrations of albumin and rapid turnover protein were measured as a marker of nutritional status. Results: A significant increase in serum levels was seen in patients with esophageal, gastric, and colorectal cancers compared to healthy volunteers. Levels of VEGF were inversely correlated with serum concentrations of albumin, prealbumin and retinol-binding protein. Serum concentrations of VEGF were inversely correlated with the production of interleukin (IL)-12 and correlated with MDSC. VEGF levels also correlated with neutrophil count and neutrophil/lymphocyte count, and correlated inversely with lymphocyte count. Serum VEGF levels were then divided about a cutoff of 500 pg/ml, with levels of prealbumin and retinol-binding protein significantly decreased in patients with higher VEGF levels. Stimulation index and IL-12 production were significantly decreased in the group with higher VEGF levels, and MDSC counts tended to be higher in this group. Conclusions: These results demonstrated that increased production of VEGF correlated with systemic inflammation, nutritional impairment and inhibition of cell-mediated immunity involving MDSCs. An inactivation of dendritic cells may be occurring by the activation of MDSC. Anti-VEGF therapy may be of importance in treating digestive system cancers.

Assessment of the usefulness of β2-microglobulin and retinol binding protein for the purpose of testing kidney function in HIV-positive patients

AimThe aim of the study was to assess the importance and usefulness in everyday clinical practice of the urinary concentrations of β-microglobulin (β2M) and retinol binding protein (RBP) in evaluation of the renal function in HIV-positive patients. BackgroundKidney proximal tubule cells are the most prone to the damage and for low molecular-weight proteins as β-microglobulin (β2M) and retinol binding protein (RBP) are sensible markers of the pathology of this part of the nephron. Materials and methodsUrine collected from 86 HIV-positive patients consulted in HIV/AIDS Outpatients Clinic in Wroclaw. ResultsIn the group with decreased base-line GFR on tenofovir β2M level was statistically significant higher than in group on tenofovir with normal base-line GFR (p≤0.05), in group on other antiretroviral treatment (p≤0.001) and in cART-naïve patients (p≤0.001). Mean RBP levels in groups on tenofovir both with decreased and normal baseline GFR were statistically significant higher (p≤0.01; p≤0.01) than in controls. There is statistically significant (p≤0.05) negative linear correlations between the urinary concentrations of β2M and RBP and GFR as well as between urinary β2M and serum creatinine level (p≤0.05) in a group of patients receiving cART with tenofovir. Conclusionβ2M and RBP concentrations in urine may become useful in diagnosis of renal failure and are more sensitive than the standard determination of creatinine in plasma and eGFR in patients treated with tenofovir.The determination of the excretion of β2M seems a better measurement of tenofovir nephrotoxicity than RBP.

SERUM LEVELS OF ADIPOCYTE FATTY ACID BINDING PROTEIN 4 AND RETINOL BINDING PROTEIN 4 AS BIOMARKERS FOR EARLY DETECTION OF DIABETIC NEPHROPATHY IN TYPE 2 DIABETES

Background: Adipocyte fatty acid binding protein 4(A-FABP4) and retinol binding protein 4(RBP4) are recently discovered adipokines, which are members of lipocalin family. Both adipokines have been proposed to be important markers for metabolic syndrome and diabetes mellitus . Diabetic nephropathy is a leading cause of chronic kidney disease in patient starting renal replacement therapy and is associated with increased cardiovascular mortality . Objective: To study serum A-FABP4 and RBP4 levels in patients with type 2 DM with different stages of diabetic nephropathy and to investigate whether serum A-FABP4 and RBP4 could be used as biomarkers-in single or combination-for early detection of diabetic nephropathy. Subjects and methods: 60 subjects were included in this study ,they were divided into six groups according urinary albumin excretion(UAE) and glomerular filtration rate (GFR) Group 1 (Control group) consists of 10 patients who are normo-albuminuric with normal GFR . Group 2 consists of 10 patients who are normoalbuminuric with increased GFR>120 Group 3 consists of 10 patients who are microalbuminuric i.e. UAE 30-300 mg/day. Group 4 consists of 10 patients who are macroalbuminuric i.e. UAE ≥ 300 mg/day without renal impairment (normal creatinine and GFR > 90 ml/min/1.73m²). Group 5 consists of 10 patients who are macroalbuminuric with renal impairment and declining GFR <90 ml/min/1.73m². Group 6 consists of 10 patients who are end-stage renal disease (GFR <15 ml/min/1.73m²). Measurement of serum AFABP4 , serum RBP4 , UAE, GFR were done for every subject Results: There was significant increase in the serum level of AFABP4 and RBP4 among different stages of diabetic nephropathy and there was significant difference between microalbuminuric group and normoalbuminuric group so both biomarkers can be used for early detection of diabetic nephropathy. Both AFABP4 and RBP4 correlated positively with UAE and negatively with GFR. Conclusion: High circulating AFABP4 and RBP4 concentrations were demonstrated in early diabetic nephropathy in type 2 DM. AFABP4 and RBP4 increased significantly with the progression of diabetic nephropathy. Large scale multicenter and prospective studies are necessary to gather a definitive support that these adipokines might be directly involved in early detection of diabetic nephropathy and in impairment of kidney function in type 2 DM. Key words : AFABP4 ,RBP4 ,diabetic nephropathy ,type 2 diabetes

Proteomics analysis for finding serum markers of ovarian cancer.

A combination of peptide ligand library beads (PLLB) and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS) was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4) is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value 89.13 ± 1.67 ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85 ± 2.38 ng/mL). Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.

Decreased retinol-binding protein 4 in the sera of patients with end-stage renal disease after kidney transplantation.

Retinol-binding protein 4 (RBP4) is a novel adipokine that has been associated with insulin resistance and type 2 diabetes. Patients with end-stage renal disease (ESRD) have very high serum RBP4 levels. However, whether successful kidney transplantation alleviates these elevated serum RBP4 levels is unclear. The serum RBP4 levels of 24 ESRD patients were determined before transplantation and at 1 day, 1 week, and 1 month after kidney transplantation. The control group included 22 healthy subjects. Serum RBP4 concentrations were measured using a commercial kit via the immunologic turbidimetric method, and were related to biomarkers for renal and liver function. The serum RBP4 level of ESRD patients before kidney transplantation (160.8 ± 29.1 mg/L) was approximately 7-fold higher than that of normal controls (22.6 ± 11.0 mg/L; P = 0.000). The serum RBP4 level before transplantation was significantly higher than that at 1 day (65.3 ± 28.4 mg/L), 1 week (48.3 ± 22.9 mg/L), and 1 month after transplantation (53.1 ± 25.5 mg/L; P = 0.000). However, these values were still higher than those of controls (P = 0.000). Univariate regression analysis showed that the percent changes in serum RBP4 concentration before and after kidney transplantation were positively correlated with serum creatinine, blood urea nitrogen, phosphate, and pre-albumin concentrations and negatively correlated with the estimated glomerular filtration rate. The serum RBP4 concentration of patients with ESRD decreased significantly after kidney transplantation; therefore, we found that serum RBP4 concentration was related to renal function.

Anthropometric and micronutrient status of school-children in an urban West Africa setting: a cross-sectional study in Dakar (Senegal).

BackgroundUrban areas in West Africa are not immune to undernutrition with recent urbanization and high food prices being important factors. School children often have a poor nutritional status, potentially affecting their health and schooling performance. Yet, generally school children do not benefit from nutrition programs. The objective of the study was to assess the anthropometric and micronutrient status of children from state schools in the Dakar area.MethodsSchool children (n = 604) aged from 5 to 17 y (52.5% girls, 47.5% ≥10 y) were selected through a two-stage random cluster sample of children attending urban primary state schools in the Dakar area (30 schools × 20 children). The prevalence of stunting (height-for-age<−2 z-scores) and thinness (BMI-for-age<−2 z-scores, WHO 2006, and three grades of thinness corresponding to BMI of 18.5, 17.0 and 16.0 kg/m2 in adults) were calculated from weight and height. Hemoglobin, plasma concentrations of ferritin (FER), transferrin receptors (TfR), retinol binding protein (RBP), and zinc, and urinary iodine concentrations were measured. Correction factors were used for FER and RBP in subjects with inflammation determined with C-reactive protein and α1-acid-glycoprotein.Results4.9% of children were stunted, 18.4% were thin, 5.6% had severe thinness (BMI-for-age<−3 z-scores). Only one child had a BMI-for-age>2 z-scores. Prevalence of anemia, iron deficiency and iron deficiency anemia was 14.4%, 39.1% and 10.6% respectively. 3.0% had vitamin A deficiency, 35.9% a marginal vitamin A status, and 25.9% zinc deficiency. Urinary iodine was <50 µg/L in 7.3% of children and ≥200 µg/L in 22.3%. The prevalence of marginal vitamin A, zinc deficiency, high TfR was significantly higher in boys than in girls (P<0.05). Height-for-age and retinol were significantly lower in participants ≥10 y and <10 y respectively.ConclusionUndernutrition, especially thinness, iron and zinc deficiencies in school children in the Dakar area requires special targeted nutrition interventions.

The Relative Dose Response Test Based on Retinol-Binding Protein 4 Is Not Suitable to Assess Vitamin A Status in Very Low Birth Weight Infants

Background: The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. Objectives: This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. Methods: This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. Results: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5% (-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). Conclusion: The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants.

Crosstalk between circulating peroxisome proliferator-activated receptor gamma, adipokines and metabolic syndrome in obese subjects

BackgroundPeroxisome proliferator-activated receptor gamma (PPARγ) has direct and indirect function in adipokines production process. We aimed to assess the possible influence of circulating PPARγ on relative risk of metabolic syndrome and also examine the association between circulating PPARγ and adipokines levels among obese subjects.MethodsA total of 96 obese subjects (body mass index (BMI) ≥30) were included in the current cross-sectional study. We assessed the body composition with the use of Body Composition Analyzer BC-418MA - Tanita. The MetS (metabolic syndrome) was defined based on the National Cholesterol Education Program Adult Treatment Panel III. All baseline blood samples were obtained following an overnight fasting. Serum concentrations of adipokines including Retinol binding protein 4 (RBP4), omentin-1, vaspin, progranulin, nesfatin-1 and circulating PPARγ was measured with the use of an enzyme-linked immunosorbent assay method. Statistical analyses were performed using software package used for statistical analysis (SPSS).ResultsWe found main association between circulating PPARγ and body composition in obese population. The risk of metabolic syndrome in subjects with higher concentration of PPARγ was 1.9 fold in compared with lower concentration of PPARγ after adjustment for age, sex and BMI. There was significant association between PPARγ and adipokines, specially nesfatin-1 and progranulin. Defined adipokines pattern among participants demonstrated the markedly higher concentration of vaspin, RBP4 and nesfatin-1 in participants with MetS compared to non-MetS subjects.ConclusionsIt appears all of studied adipokines might have association with PPARγ level and might simultaneously be involve in some common pathway to make susceptible obese subjects for MetS.

Reduced serum retinol-binding protein levels in patients with de novo acute myeloid leukaemia

Retinol-binding protein (RBP) has been used as a nutritional index for children with acute myeloid leukaemia (AML) in previous studies. However, no studies have yet examined RBP levels in AML patients from all age groups. In this study, AML patients presented with lower RBP concentrations than healthy control subjects and patients with benign haematopathies. A negative association was observed between serum RBP level and peripheral white blood cell count in M4 and M5 AML patients. Moreover, patients carrying the FLT3-ITD mutation and young patients had lower RBP levels than those lacking this mutation and elderly patients. In conclusion, these observations suggest that aberrant retinol levels may be associated with AML.

Effects of prior acute exercise on circulating cytokine concentration responses to a high-fat meal

High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the effects of prior exercise on the responses of circulating tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy men were studied before and 4 h after ingestion of a high-fat meal either with or without ∼50 min of endurance exercise at 70% of VO2 max on the preceding day. In response to the high-fat meal, lower leptin and higher VEGF, bFGF, IL-6, and IL-8 concentrations were evident (P < 0.05 for all). There was no effect of the high-fat meal on PlGF, TNF-α, or RBP4 concentrations. We found lower leptin concentrations with prior exercise (P < 0.05) and interactive effects of prior exercise and the high-fat meal on sFlt-1 (P < 0.05). The high-fat meal increased IL-6 by 59% without prior exercise and 218% with prior exercise (P < 0.05). In conclusion, a prior bout of endurance exercise does not affect all high-fat meal–induced changes in circulating cytokines, but does affect fasting or postprandial concentrations of IL-6, leptin, and sFlt-1. These data may reflect a salutary effect of prior exercise on metabolic responses to a high-fat meal.

Sensitive ECL immunosensor for detection of retinol-binding protein based on double-assisted signal amplification strategy of multiwalled carbon nanotubes and Ru(bpy)32+ doped mesoporous silica nanospheres

A novel electrochemiluminescence (ECL) strategy based on the sandwich-type immunosensor for sensitive detection of retinol-binding protein (RBP) was developed. The primary antibody anti-RBP was immobilized onto multiwalled carbon nanotubes (MWCNTs), which have large surface area and high electrical conductivity. The RBP antigen and Ru–Nafion@SiO2-labeled secondary antibody were then successively conjugated to form sandwich-type immunocomplexes through the specific interaction between antigen and antibody. The ECL signal amplification was significantly improved due to the synergistic effect of MWCNTs and mesoporous silica nanospheres (mSiO2). The developed ECL immunosensor exhibited high sensitivity and specificity for the detection of RBP and responded linearly to the clinically-relevant concentration of RBP from 78 to 5000ngmL−1. Moreover, the MWCNT-based ECL immunosensor displayed excellent stability and reproducibility, as well as successfully achieved the detection of RBP in patient urine samples with desirable results. The present work provided a promising technique for the clinical screening of RBP and point-of-care diagnostics.