Plasma Retinol-binding Protein Research Articles

Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients

BackgroundRetinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients.MethodsThis prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients.ResultsRBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71–22.92) versus 9.59 (6.57–13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7.ConclusionPlasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy.

Carboranes are promising agents for applications in boron neutron capture therapy (BNCT), but their hydrophobicity prevents their use in physiological environments. Here, by using reverse docking and molecular dynamics (MD) simulations, we identified blood transport proteins as candidate carriers of carboranes. Hemoglobin showed a higher binding affinity for carboranes than transthyretin and human serum albumin (HSA), which are well-known carborane-binding proteins. Myoglobin, ceruloplasmin, sex hormone-binding protein, lactoferrin, plasma retinol-binding protein, thyroxine-binding globulin, corticosteroid-binding globulin and afamin have a binding affinity comparable to transthyretin/HSA. The carborane@protein complexes are stable in water and characterized by favorable binding energy. The driving force in the carborane binding is represented by the formation of hydrophobic interactions with aliphatic amino acids and BH-π and CH-π interactions with aromatic amino acids. Dihydrogen bonds, classical hydrogen bonds and surfactant-like interactions also assist the binding. These results (i) identify the plasma proteins responsible for binding carborane upon their intravenous administration, and (ii) suggest an innovative formulation for carboranes based on the formation of a carborane@protein complex prior to the administration.

P203 PLASMA TRANSTHYRETIN FORMS IN PATIENTS WITH WILD–TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS: INFLUENCED OF TAFAMIDIS TREATMENT

Abstract Introduction Transthyretin (TTR) is a plasma protein that transports thyroxin and retinol complexed to retinol–binding protein (RBP). TTR misfolding and aggregation can lead to the extracellular deposition of amyloid in the myocardium, causing TTR cardiac amyloidosis (ATTR–CA). Aim of this study is to develop a native electrophoretic method to characterize circulating TTR forms in plasma samples of ATTR–CA patients, before and after administration of tafamidis, a TTR stabilizer. Material &amp; Methods Plasma samples from patients affected by wild–type ATTR amyloidosis (ATTRwt, n=10) were collected before (T0) and during tafamidis treatment at 14, 30 and 90 days. Plasma samples of sex– and age–matched healthy controls (n=6) were also collected. All samples were separated on a native 4–20% Tris–Gly polyacrylamide gel. Western blot analysis was performed with anti–TTR or anti–RBP antibodies. Proteins were detected by Clarity ECL substrate. ImageLab software was used for image acquisition and densitometric analysis of the blots. Total TTR (mg/dl) and RBP (mg/dl) were quantified by nephelometry. Results In both groups, the most represented forms were: TTR dimers or trimers (37–50kDa), TTR tetramers complexed with RBP protein in 1:1 (75kDa,) or 1:2 ratio (100kDa), and high molecular weight aggregates (&amp;gt;150kDa). RBP protein was detectable in association with TTR tetramers and some of the TTR aggregates (250kDa, 480kDa). Based on TTR electrophoretic pattern at T0, patients could be divided in 2 groups: ATTR–1, characterised by the presence of TTR tetramers (55kDa), and ATTR–2, characterised by its absence. The ATTR–1 group showed also higher levels of total TTR in comparison with ATTR–2 (mean±SD 25.5±3.8, 16.6±4.2 respectively, p=0.004), while plasma RBP levels were similar (5.1±0.7, 5.1±1.4 respectively). The electrophoretic patterns of ATTR–1 at T0, as well as TTR and RBP levels were comparable to those of controls (TTR 22.6±3.8, RBP 4.4±0.9). Tafamidis treatment was associated with a progressive increase of total TTR levels both in ATTR–1 and –2 (T90 31.4±5.8, 28.7±6.8) but the 2 groups continued to be distinguishable by the electrophoretic pattern. Conclusions The native electrophoresis allowed us to detect diverse circulating TTR forms and to classify patients in 2 groups according to their electrophoretic pattern. TTR quali/quantitative evaluation by electrophoresis could represent a valid tool to assess the individual pharmacological response to tafamidis.

Assessment of Vitamin A Status in Patients with Iron Deficiency Anemia

Introduction: Iron and vitamin A deficiency are two very prevalent and easily preventable nutrient deficiencies. This study was conducted to assess vitamin A status in patients with iron deficiency anemia and to further study the correlation of vitamin A status with biochemical markers of iron deficiency. Materials and Method: Eighty patients with iron deficiency anemia were enrolled and investigated for a complete blood count, an iron profile, liver, and kidney function tests and plasma retinol binding protein levels. The mean age of patients was 31.14 ± 11.33 years, with a range of 16 to 62 years. Results: Mean hemoglobin was 7.19 ± 2.1 g/dL. Serum iron, ferritin, and transferrin saturation were low in all patients, while total iron binding capacity (TIBC) was elevated in only 74 patients (94.81%). Nineteen patients (23.8%) had vitamin A deficiency, with a mean retinol binding protein (RBP) 0.53 ± 0.13 µmol/L. Vitamin A deficient patients had a mean hemoglobin of 6.8±2.14 gm/dL, mean corpuscular volume (MCV) 71.35 ± 8.86 fL, a mean corpuscular hemoglobin (MCH) 19.43±4.36 pg, mean corpuscular hemoglobin concentration (MCHC) 25.44±4.92 gm/dL, serum iron of 28.21 ± 9.73 mcg/dL, serum ferritin 13.04 ± 12.41 ng/mL, transferrin saturation 6.81 ± 3.07%, and TIBC 427.85 ± 78.57 mcg/dL. Among vitamin A deficient patients, RBP had positive correlation with serum iron and transferrin saturation; while, simultaneously showing negative correlation with serum ferritin and TIBC. Conclusion: Vitamin A deficiency affects iron metabolism, causing abnormal iron trapping and systemic iron deficiency, thus worsening the clinical profile of iron deficiency anemia. This study guides us to screen iron deficiency anemia patients for the concomitant vitamin A deficiency for efficient treatment of such patients.

Longitudinal Change of Plasma Retinol-Binding Protein 4 and its Relation to Neurological-Function Recovery, Relapse, and Death in Acute Ischemic Stroke Patients.

Retinol-binding protein 4 (RBP4) promotes dyslipidemia, insulin resistance, inflammation, and atherosclerosis, etc. which may participate in the progression of acute ischemia stroke (AIS). This study aimed to evaluate the longitudinal change of RBP4 after disease onset and its correlation with prognosis in AIS patients. Plasma RBP4 was measured by enzyme-linked immunosorbent assays in 402 AIS patients at admission, one day (D1), 3 days (D3), 7 days (D7), and 30 days (D30) after admission; and in 100 healthy controls after enrollment. The neurological-function recovery was evaluated by the modified Rankin Scale (mRS) at 3 months (M3); disease relapse and death were also recorded during a median 20-month follow-up in AIS patients. Our study revealed that RBP4 was elevated in AIS patients compared with healthy controls. RBP4 was related to a history of diabetes mellitus, a history of cardiovascular disease, and elevated National Institutes of Health Stroke Scale score in AIS patients. Longitudinally, RBP4 was increased from admission to D1/D3, then reduced gradually to D30 in AIS patients. Notably, RBP4 at admission and D1 was elevated in AIS patients with mRS > 2 compared to those with mRS ≤ 2. Meanwhile, RBP4 at admission, D1, D3, D7, and D30 were all higher in AIS patients occurred relapse than those without; RBP4 at D3, D7, and D30 were also higher in AIS patients who died later than those who survived. In conclusion, plasma RBP4 originally elevates and continuously decreases during disease, which forecasts neurological-function recovery status, relapse, and death risk of AIS.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials

ABSTRACTBackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers.ResultsSQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics.ConclusionsSQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Plasma Retinol Binding Protein 4 as a Biomarker for Detecting Progressive Stroke and Prediction of Early Prognosis in Patients with Acute Ischemic Stroke.

Participants of this retrospective study were 234 patients with AIS within the 48 h onset of disease. The primary endpoint was to ascertain if there was PS through the National Institute of Health stroke scale (NIHSS); the early prognosis was confirmed through the modified Rankin scale score (mRS) at discharge or 14 days after the onset of stroke, and the significance of demographic characteristics and clinical data was determined. In this study, 43 of 234 patients demonstrated PS. The level of plasma RBP4 in patients with progressive stroke was significantly lower (29 mg/L, 22.60-40.38 mg/L) than that without progression (38.70 mg/L, 27.28-46.40 mg/L, P = 0.003). In patients with lower plasma RBP4, the proportion of patients with progression (χ2 = 9.63, P = 0.008) and with mRS scores ≥2 (χ2 = 6.73, P = 0.035) was significantly higher. Multivariate logistic regression analysis showed that a lower RBP4 level on admission was an independent risk factor for progressive stroke during hospitalization with an OR value of 2.70 (P = 0.03, 95% CI: 1.12-6.52). A low plasma RBP4 level on admission could be an independent risk factor of PS during hospitalization.

Synthesis, X-Ray Structure, Hirshfeld Surface Analysis, DFT Calculations, and Molecular Docking Studies of Nickel(II) Complex with Thiosemicarbazone Derivative.

This article presents both experimental and computational study of a new Ni(II) complex, namely, bis{2-(2-trifluoromethylbenzylidene)hydrazine-1-carbothioamido-κ2N2, S}nickel(II) (abbreviate as NiL2). The complex was synthesized and well characterized using various spectroscopic methods. The single X-ray crystallographic study revealed a distorted square planar geometry around Ni(II) metal ion centre in which the angles deviated from ideal 90° with a maximum value of 6.57° occupied by nitrogen and sulphur donor atoms. The theoretical bond lengths and angles for the NiL2 complex were obtained by using the B3LYP level of density function theory (DFT) with LANL2DZ/6-311G (d, p) basis sets. These results showed very good agreement with the experimental X-ray values. The electrophilicity index (ω = 50.233 eV) shows that the NiL2 complex is a very strong electrophile. In addition, strong F⋯H/H⋯F interactions with 28.5% of the total Hirshfeld surface analyses in NiL2 were obtained indicating that the complex could bind with protein effectively. Furthermore, the new NiL2 complex was docked with plasma retinol-binding protein 4 (RBP4) (PDB id: 5NU7), which implied that the NiL2 complex bound to Tyrosine 133 and Aspartate 102 amino acids via N-H intermolecular hydrogen bonds.

Exploring the mediating role of serum retinol-binding protein 4 in the relationship between sleep quality and insulin resistance in pregnant women

AimsWe aimed to explore the mediating role of plasma retinol-binding protein 4 (RBP4) in the relationship between sleep quality and insulin resistance (IR) among pregnant women. MethodsWe conducted a cross-sectional study including 263 pregnant women in the first trimester. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI). The ELISA and homeostasis model assessment (HOMA) was used to analyze plasma RBP4 and estimate IR. The mediating model was used to analyze the mediating role of RBP4 in the relationship between PSQI score and IR. ResultsIn the multivariable linear regression model, the three terms were positively related with each other, PSQI score was positively associated with IR levels (β = 0.55, p < 0.05). In the mediating model, RBP4 levels mediated completely the relationship between PSQI scores and IR levels (β = 0.29, p < 0.0001). The indirect effect of RBP4 in the relation between sleep quality and IR explained 89.10% of total effect. ConclusionsRPB4 may play a complete mediating role in the relation between sleep quality and insulin resistance in early pregnancy. Improvements in sleep quality in the first trimester may provide a pathway to reduce plasma RBP4, which is beneficial for less IR and GDM prevention.

Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status, Anemia, and Dietary Intake in South African Schoolchildren.

The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤ 40 µg/L), n = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin > 40 µg/L, hemoglobin ≥ 115 g/L), n = 41; (3) children without HIV (HIV-ve) and low iron stores, n = 45; and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p < 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR > 8.3 mg/L) (95% CI: 1.03–5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4–5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6–27, p < 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B12, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as NCT03572010.

Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis

Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease.

Ten2Twenty-Ghana: Study Design and Methods for an Innovative Randomized Controlled Trial with Multiple-Micronutrient-Fortified Biscuits among Adolescent Girls in Northeastern Ghana.

ABSTRACTInvesting in adolescent girls’ nutrition is vital for health and for breaking the intergenerational cycle of malnutrition and deprivation, but limited knowledge on the type, timing, and efficacy of interventions delays progress. We describe the design of a 26-wk randomized placebo-controlled trial with multiple-micronutrient–fortified biscuits (MMBs) among adolescent girls in northeastern Ghana. Apparently healthy, premenarche (n = 312) and postmenarche (n = 309) girls (10–17 y) were randomly assigned to receive the following for 5 d/wk: 1) MMBs (fortified with 11 vitamins and 7 minerals) or 2) unfortified biscuits. Data included plasma micronutrient status, anthropometry, body composition, cognitive function, psychosocial health, fertility, dietary intake, and sociodemographic and socioeconomic covariates, complemented with in-depth interviews (n = 30) and 4 focus group discussions. We hypothesized an increase in plasma ferritin and retinol-binding protein with a resultant increase in hemoglobin, cognition, vertical height, and psychosocial health. Our study seeks to investigate the efficacy and optimal timing of a multiple-micronutrient food intervention program for adolescent girls. The RCT was registered prospectively with the Netherlands Clinical Trials Register (NL7487).

Changes in Retinol Binding Protein 4 Level in Undernourished Children After a Nutrition Intervention Are Positively Associated With Mother's Weight but Negatively With Mother's Height, Intake of Whole Milk, and Markers of Systemic Inflammation: Results From a Community-Based Intervention Study.

Background:The changes of plasma retinol binding protein 4 (RBP4) level after a nutrition intervention can indicate the metabolic changes associated with the delivered intervention.Objective:We investigated the changes in plasma RBP4 level among 12- to 18-month-old children after a nutrition intervention and measured its association with subcutaneous adiposity, maternal characteristics, and inflammation.Methods:Data of 520 undernourished children (250 of them had length-for-age Z score [LAZ] <−1 to −2 and 270 had LAZ score <−2) were collected from the Bangladesh Environmental Enteric Dysfunction study conducted in Dhaka, Bangladesh. Multivariable linear regression and generalized estimation equations (GEE) modeling techniques were used to measure the association.Results:At baseline, median RBP4 level was 19.9 mg/L (interquartile range [IQR]: 7.96), and at the end of the intervention, it was 20.6 mg/L (IQR: 9.06). Percentage changes in plasma RBP4 level were not significantly associated (P > .05) with the percentage changes in child’s height, weight, and subcutaneous adiposity. But maternal height (regression coefficient, β = −1.62, P = .002) and milk intake (β = −0.05, P = .01) were negatively and maternal weight was positively associated (β = 0.56, P = .03) with the changes in RBP4 levels. The GEE models revealed negative association of RBP4 levels with C-reactive protein (CRP; β = −0.14, P < .05) and α-1-acid glycoprotein (AGP; β = −0.03, P < .05).Conclusion:Children whose mothers were taller experienced less increase in plasma RBP4 level, and children whose mothers had a higher weight experienced more increase in the RBP4 level from baseline. We have also found that CRP and AGP levels and intake of whole milk were negatively associated with the plasma RBP4 level.

1986-P: Plasma Retinol Binding Protein 4 and Adipsin Levels Were Not Altered after Gastric Sleeve Surgery in Adult Male Population

Background: Bariatric or weight loss surgery provides the most substantial and sustainable weight loss in individuals with obesity. Caloric restriction and malabsorption are not the only mechanisms by which bariatric surgery reduces body weight and improves glycemic control. Alterations in the secretion and activity of hormones are also the contributory mechanisms in bariatric surgery. We evaluated the levels of retinol binding protein 4 (RBP4) and adipsin after gastric sleeve surgery and their relationship with insulin and lipid parameters. Method: Thirty-three obese (BMI &amp;gt; 38.3) healthy male subjects age ranged from 25 to 50 years were selected for this study. Plasma levels of RBP4 and adipsin were analyzed before and six months after gastric sleeve surgery by ELISA, along with plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and lipid profile. Results: Circulating RBP4 was not significantly changed by bariatric surgery (4382.85±7.03 ng before, and 4393.28±5.769 ng after surgery, P= 0.842), neither did adipsin (2949.68±8.16 pg before, and 2917.90±7.295 pg after surgery, P=0.535). As expected, there was a reduction in BMI, insulin levels and HOMA-IR after six months of surgery. Lipid profile analysis revealed that cholesterol, high density lipoproteins (HDL), and low density lipoproteins (LDL) levels were increased after surgery (4.26±0.027 to 5.12±0.026 mmol/L and 0.90±0.007 to 1.55±0.011 mmol/L and 2.62±0.02 to 2.98±0.022 mmol/L, P&amp;lt;0.001) respectively. However, there was no correlation between RBP4, adipsin and insulin and lipid parameters. Conclusions: Our findings do not suggest a role for RBP4 and adipsin in the improvement of insulin sensitivity in obese male population after gastric sleeve surgery. Moreover, there was no correlation between their plasma levels and either BMI, glucose, insulin, or lipid profiles. Disclosure S. Alshubrami: None. M. Iqbal: None. A. Alfadda: None. K. Alregaiey: None. Funding King Abdulaziz City for Science and Technology (1-17-03-001-0026)

A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish.

Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is, however, not expressed in systemic tissues, where there is high affinity RBP4 binding and ROL uptake. We tested the hypothesis that the second retinol binding protein 4 receptor 2 (Rbpr2), which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR-generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, which were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatment rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival.

Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study

BackgroundTo 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).MethodsPlasma 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.ResultsThe 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.ConclusionsPlasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.

Impact of Gastric Sleeve Surgery on Plasma Retinol Binding Protein 4 and Adipsin Levels in Healthy Male Population.

Objectives:Bariatric surgery provides most substantial and sustainable weight loss measures in individuals with obesity. Caloric restriction is not only intervention, changes in hormonal secretions are also leading contributory mechanisms to reduce body weight and improve the glycaemic control. The aim of this study was to evaluate the impact of gastric sleeve surgery on plasma retinol binding protein 4 (RBP4) and adipsin levels among Saudi male obese population.Methods:This prospective study was conducted in the Departments of Physiology and Surgery, College of Medicine, King Saud University. Thirty-three obese (BMI>38.3) male patients age ranged from 25 to 50 years were recruited. RBP4 and adipsin levels were analyzed before and 6-12 months after gastric sleeve surgery by ELISA along with plasma glucose, insulin, HOMA-IR and lipid profile.Results:Circulating RBP4 levels were not significantly changed by bariatric surgery (4382.85±40.35 ng before, and 4393.28±33.13 ng after surgery, p=0.842), neither did adipsin (2949.68±46.86 pg before, and 2917.90±41.90 pg after surgery, p=0.535). Segregation of study participants into two age groups, 25-35 and 35-50 years of age, revealed that before surgery older age group (35-50) had higher RBP4 levels compared to younger group (25-35) (p=0.016). However, after surgery RBP4 levels were decreased in older group but not to a significant level (p=0.174). In younger age group after surgery, there was a near significant increase in RBP4 levels (p=0.052). There were no significant changes in RBP4 levels in both age groups after surgery (p=0.461). For adipsin, there were no significant differences before and after surgery in both age groups. Insulin, BMI and HOMA-IR index were decreased after surgery, however there was no correlation with RBP4 and adipsin levels.Conclusions:The present study findings do not suggest a role for RBP4 and adipsin in the improvement of insulin sensitivity in Saudi male obese population after gastric sleeve surgery. However, a decrease in RBP4 levels in older individuals after surgery needs further investigations to understand its effect on weight and glycemic control.

Biomarkers of cadmium, lead and mercury exposure in relation with early biomarkers of renal dysfunction and diabetes: Results from a pilot study among aging Canadians

Cadmium (Cd), lead (Pb) and mercury (Hg) are known nephrotoxicants that have been associated with the risk of developing type-2 diabetes (T2D). The aim of this pilot study was to explore relations between biomarkers of Cd, Pb and Hg exposure, early urinary biomarkers of renal dysfunction (kidney-injured molecule-1 (KIM-1), N-acetylglucosaminidase and retinol-binding protein (RBP)) and plasma biomarkers deemed predictive of the risk of developing T2D (adiponectin, leptin, branched-chain and aromatic amino acids), among 70 participants (age range: (46–87 yrs)) from the Canadian Longitudinal Study on Aging (CLSA) with normal glycemic control (glycated haemoglobin ≤ 6.5%) in all but four of them. Significant (p < 0.05) Spearman correlation coefficients were obtained between: plasma adiponectin and RBP (r = 0.42), urinary Cd (r = 0.32), blood Cd (r = 0.36); KIM-1 and CdU (r = 0.33) as well as HgU (r = 0.37); RBP and isoleucine (r = -0.28), leucine (r = -0.33), tyrosine (r = -0.3) and valine (r = -0.44); CdU and isoleucine and valine (r = -0.27 for both). Multiple linear regression analyses showed that some T2D-related biomarkers are confounders of associations between RBP and Hg or Cd biomarkers. Path analyses support a mediating effect of adiponectin on the relation between urinary Cd and RBP. Concluding, this pilot study originally investigated a comprehensive set of biomarkers on complex interactions between toxic metal exposure, renal function and T2D in a group of aging Canadians. Its findings warrant further investigation of longitudinal data in a greater number of participants.

Within-individual differences in plasma ferritin, retinol-binding protein, and zinc concentrations in relation to inflammation observed during a short-term longitudinal study are similar to between-individual differences observed cross-sectionally

Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case. The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences. Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabé children aged 6-23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures. In CS models, geometric mean pF and sTfR concentrations were 8-340% greater, and RBP and pZn 2-18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar. The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853.

A Pilot, Randomized Study in Women of Nutrition-Related Clinical Chemistry at 6Weeks after Roux en Y Gastric Bypass: Comparison of Two Nutrition Support Plans.

The current pilot study tested a twofold hypothesis: some nutrition-related chemical measures change by 6weeks after Roux en Y Gastric Bypass (RNYGB); one of two nutrition support plans will prevent chemical signs of nutrition problems at 6weeks better than the other. After RNYGB, nutrition support should begin right away. However, studies on nutritional status mostly examine subjects much later. In addition, little attention has been paid to optimizing nutrition support plans. Premenopausal females scheduled for RNYGB were given either a commercially available meal replacement product (2 servings/day) + other supplements or just a new meal replacement (2 servings/day). The latter included some nutrient versions that might enhance absorption. Blood and urine samples were taken before and 6weeks after surgery. In both groups, plasma vitamin D and B12 did not change, plasma osteopontin and vascular endothelial growth factor rose, while plasma retinol binding protein and a bone resorption marker declined. Copper status changes differed between groups based on plasma ceruloplasmin. Iron status improved in both groups (ferritin to c-reactive protein ratios). With the new formulation, magnesium status may have improved, urinary potassium rose, and blood sugar fell. In the other group, a liver damage marker increased, while homocysteine decreased. Nutrition-related parameters showed varying trends 6weeks after RNYGB. Some of the trends were affected by the type of nutritional support provided.