Plasma Retinol-binding Protein 4 Research Articles

Assessment of Circulating Retinol Binding Protein-4 Levels in Patients with Compound Heterozygosity for Hb S and β-Thalassemia

Background: Retinol Binding Protein-4 (RBP-4) is a member of the lipocalin family of proteins and the major transport protein of the hydrophobic molecule retinol, also known as vitamin A, in the circulation. Expression of RBP4 is highest in the liver, where most of the body's vitamin A reserves are stored as retinyl esters. For the mobilization of vitamin A from the liver, retinyl esters are hydrolyzed to retinol, which then binds to RBP-4 in the hepatocyte. After associating with transthyretin (TTR), the retinol/RBP-4/TTR complex is released into the bloodstream and delivers retinol to tissues via binding to specific membrane receptors. While, after its dissociation from TTR and retinol release, retinol-free apo-RBP4 in the circulation is filtrated by the kidney. More than 99% of that is reabsorbed by the proximal renal tubule, which renders urinary RBP-4 a highly sensitive marker for tubular dysfunction. We and other have shown previously that the patients with Sickle Cell Disease (SCD) have deficiencies or suboptimal levels of vitamin A, while recently (Br J Haematol. 2023;doi:10.1111/bjh.18862) higher urine RBP-4 in patients with SCD especially in those with persistent albuminuria but without an association of urine RBP-4 levels with estimated glomerular filtration rate (eGFR). In this context, we aimed to investigate the potential clinical significance of circulating plasma RBP-4 levels and its association with disease features in Caucasian patients with compound heterozygosity for HbS and β-thalassemia (HbS/β thal). Patients and Methods: Ninety Caucasian adult patients with HbS/β thal at steady phase were included in the study, while 22 apparently healthy individuals of similar age and gender served as controls. None of the patients was diabetic and has received any transfusions at least 6-monthes before enrollment in the study. RBP-4 concentration was measured with an immunoturbidimetric assay applied in an automated chemistry analyzer, along with hematologic, and series of blood chemistry parameters reflecting renal, cardiac and endothelial dysfunction. eGFR values were calculated using the CKD-EPI (Cystatin C and/or Creatinine equations). Results: We found that: a) Plasma RBP-4 levels were significantly lower in patients with HbS/β thal compared to controls, 30.5±2.7mg/L (Confidence Intervals (CI): 28.8;32.2mg/mL) vs 36.3±3.6mg/L (CI: 32.7;39.9mg/mL), p<0.003. The patients with β + genotypehave higher RBP-4 levels than those with β 0 genotype (p<0.05), whereas patients treated with hydroxycarbamide(50/90) are more likely to express higher RBP-4 levels, p-trend=0.06; b) RBP-4 levels in patients with HbS/β thal correlated positively with their age, body mass index (BMI) and Hb levels (r=0.264, p=0.012; r=0.334, p=0.001 and r=0.209, p<0.05, respectively; c) RBP-4 levels in patients with HbS/β thal correlated with total bilirubin, total cholesterol, triglycerides and uric acid (r=-0.452, p<0.001; r=0.395, p=0.004; r=0.292, p=0.015 and r=0.435, p<0.001, respectively); d) RBP-4 levels in patients with HbS/β thal correlated negatively with eGFR values rho=-0.360, p=0.003 and hs-CRP concentrations r=-0.309, p=0.004 and e) No correlations were found between RBP-4 levels with markers of cardiac and endothelial dysfunction such as High Sensitivity Troponin T, Growth Differentiation Factor-15, von Willebrand factor antigen, Α Disintegrin and Metalloproteinase with Thrombospondin Type 1 Motif 13 antigen and P-Selectin, as well as with number of vaso-occlusive crisis and mean pulmonary arterial pressure in the patients. Conclusions: These findings demonstrate a multifactorial role of RBP-4 in patients with HbS/β thal as the circulating levels of the protein correlate significantly with markers of erythropoiesis, inflammation and renal function. It is unclear of this study if RBP-4 has any specific functions in patients with HbS/β thal. However, RBP-4 should be more investigated in order to determine its clinical significance and in the case of sickle cell nephropathy both plasma and urine measurements should be considered.

Significance of Plasma Irisin, Adiponectin, and Retinol Binding Protein-4 Levels as Biomarkers for Obstructive Sleep Apnea Syndrome Severity.

Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder that is caused by the reduction or cessation of airflow in the upper airway. Irisin, retinol-binding protein-4 (RBP-4), and adiponectin are the three significant factors in the metabolic process of the human body. The objective of this study was to investigate whether plasma irisin, RBP-4, and adiponectin levels are associated with the severity of OSAS. According to inclusion and exclusion criteria, 125 patients with OSAS and 46 healthy, gender-matched controls were included in this study. The patients were classified according to the apnea hypopnea index (AHI) as 14 mild cases (5 < AHI < 15), 23 moderate OSAS cases (15 < AHI < 30), and 88 severe OSAS cases (AHI > 30). The plasma irisin, RBP-4, and adiponectin levels were measured and compared between groups. RBP-4 levels were higher in severe OSAS compared to other groups, and irisin levels were significantly lower in severe OSAS compared to other groups. There was a negative correlation between irisin and RBP-4 (r = -0.421; p < 0.001), and irisin and AHI (r = -0.834; p < 0.001), and a positive correlation between irisin and adiponectin (r = 0.240; p = 0.002). There was a negative correlation between RBP-4 and adiponectin (r = -0.507; p < 0.001) and a positive correlation between RBP-4 and AHI (r = 0.473; p < 0.001). As a predictor of OSAS, adiponectin showed the highest specificity (84.8%) and RBP-4 the highest sensitivity (92.0%). Circulating adiponectin, irisin, and RBP-4 may be new biomarkers in OSAS patients in addition to risk factors such as diabetes, obesity, and hypertension. When polysomnography is not available, these parameters and clinical data can be used to diagnose the disease. As a result, patients with an AHI score greater than thirty should be closely monitored for metabolic abnormalities.

RBP4-based Multimarker Score: A Prognostic Tool for Adverse Cardiovascular Events in Acute Coronary Syndrome Patients.

Retinol binding protein 4 (RBP4) has been implicated in the progression of cardiovascular diseases. However, its association with major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) remains obscure. Here, we examined the prognostic value of baseline RBP4 and its derived multimarker score for MACEs in ACS patients. A total of 826 patients with ACS were consecutively recruited from the department of cardiology and prospectively followed up for a median of 1.95 years (interquartile range, 1.02-3.25 years). Plasma RBP4 was measured using enzyme-linked immunosorbent assay. Adjusted associations between RBP4 and its derived multimarker score (1 point was assigned when RBP4 ≥ 38.18μg/mL, left ventricular ejection fraction [LVEF] ≤ 55%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥ 450 ng/L, estimated glomerular filtration rate [eGFR] ≤ 90 mL/min/1.73 m2, and age ≥60) with MACEs were analyzed. In total, 269 ACS patients (32.57%) experienced MACEs. When patients were grouped by multimarker score (0-1, n = 315; 2-3, n = 406; 4-5, n = 105), there was a significant graded association between RBP4-based multimarker score and risk of MACEs (intermediate score (2-3): HRadj: 1.80; 95% CI, 1.34-2.41; high score (4-5): HRadj: 3.26; 95% CI, 2.21-4.81) and its components (P < .05 for each). Moreover, the prognostic and discriminative value of the RBP4-derived multimarker score remained robust in ACS patients with various high-risk anatomical or clinical characteristics. The RBP4-derived 5-item score serves as a useful risk stratification and decision support for secondary prevention in patients with ACS.

Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study

BackgroundShift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level.MethodsThe current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models. ResultsThe prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01–2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P < 0.001). Adjusting the age, gender, BMI, family income, tobacco smoking, alcohol drinking and PSQI, hailed shift work as a risk factor for T2DM (OR = 1.91, 95% CI: 1.17–3.14). The pairwise comparison revealed significant differences in RBP4 levels across different groups: shift and non-shift workers both with and without T2DM (P < 0.001). The RBP4 level of the shift group without T2DM was higher than the non-shift group without T2DM (P < 0.05). The levels of RBP4 level in shift and non-shift groups with T2DM was higher than those without T2DM (P < 0.05). The multivariate linear mixed model showed that when age, gender, BMI, diabetes, PSQI, family income, smoking and drinking remained unchanged, the RBP4 level of the shift workers increased by an average of 9.51 μg/mL compared with the day workers.ConclusionsShift work is associated with an increased risk of T2DM and high levels of RBP4. Follow-up of RBP4 could facilitateearly detection of T2DM among shift workers.

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.

Association between Circulating Retinol Binding Protein 4, Body Mass Index, and Biomarkers of Environmental Enteric Dysfunction among Slum-Dwelling Lean Adults in Bangladesh.

The relationship of retinol binding protein 4 (RBP4) with biomarkers of intestinal health and gut integrity in adults is unknown. We sought to determine the correlation between plasma RBP4 level and BMI and investigate the relationship of circulating RBP4 concentration with biomarkers of environmental enteric dysfunction among lean adults (body mass index [BMI] <25.0 kg/m2) in Bangladesh. Overall, 270 adults (135 undernourished with a BMI <18.5 kg/m2 and 135 healthy controls with a BMI between 18.5 and 24.9 kg/m2) aged 18 to 45 years were evaluated. Multivariable linear regression was performed to test the association between RBP4 and fecal biomarkers of impaired gut health. RBP4 concentration was positively correlated (rho = 0.27, P < 0.001) with BMI and was significantly higher in healthy controls than undernourished adults (P < 0.001), in male than female (P < 0.001), and also in employed (P < 0.001), smokers (P = 0.048) and participants with low Self-Reporting Questionnaire (SRQ)-20 scores (an instrument to screen mental health disorders) (P = 0.049). Statistically significant negative correlations were observed between RBP4 and fecal biomarkers of gut enteropathy including myeloperoxidase (rho = -0.23, P < 0.001), neopterin (rho = -0.30, P < 0.001), and alpha-1 anti-trypsin (rho = -0.21, P < 0.001). Multivariable linear regression analysis showed that increased RBP4 concentration was associated with a significant reduction in fecal neopterin (coefficient = -0.95; 95% confidence interval: -1.44 to -0.45]; P < 0.001) after adjustment for age, sex, nutritional status at enrollment, education, dietary diversity score, SRQ-20 score, improved sanitation, household animal exposure, and alpha-1-acid glycoprotein. The study findings revealed an inverse relationship of plasma RBP4 concentration with fecal biomarkers of altered gut health among slum-dwelling lean adults in Bangladesh.

RBP4 Is Associated With Insulin Resistance in Hyperuricemia-Induced Rats and Patients With Hyperuricemia.

ObjectiveHyperuricemia (HUA) is strongly associated with abnormal glucose metabolism and insulin resistance (IR). However, the precise molecular mechanism of HUA-induced IR is still unclear. Retinol binding protein 4 (RBP4) has been shown to induce IR in type 2 diabetes mellitus. This study was designed to clarify the relationship between RBP4 and HUA-induced IR and its potential mechanisms.MethodsPatients with HUA were collected to detect the levels of plasma RBP4 and clinical biochemical indicators. Rats were fed with 10% high yeast and oteracil potassium (300 mg/kg) via intraperitoneal injection once daily for eight weeks, and gavage with adenine (100 mg/kg) once daily from the fifth week to induce the HUA model. Glucose consumption testing was performed to determine the capacity of glucose intake and consumption in 3T3-L1 adipocytes. Real-time polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA and protein level of RBP4 and insulin receptor substrate-phosphatidylinositol 3-kinase-active protein kinase (IRS/PI3K/Akt) signaling pathway-related proteins.ResultsThe levels of plasma RBP4 in both HUA patients and HUA rat models were significantly higher than that in the control groups. The level of plasma RBP4 was positively correlated with plasma uric acid, creatinine, fasting insulin, IR index, total cholesterol and triglyceride levels in patients with HUA. In HUA rats, the level of plasma RBP4 was positively correlated with plasma uric acid, IR index, and triglycerides. HUA rats also exhibited IR. After inhibition of RBP4 expression, the phosphorylation levels of the IRS/PI3K/Akt signaling pathway were increased, and IR was significantly improved.ConclusionHUA induced IR both in vitro and in vivo. RBP4 may be involved in HUA-induced IR by inhibiting IRS/PI3K/Akt phosphorylation. Our findings may provide a new insight for the treatment of IR caused by HUA.

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.

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.

Plasma RBP4 Level in Association with Body Composition, Metabolic Profile, STRA6 and RBP4 Gene Polymorphisms in Obese Romanian Children.

BackgroundPediatric obesity continues to remain a serious health concern which has significantly increased the morbidity risk in adulthood. Recent studies have analyzed the impact of the two adipokines, RBP4 (retinol binding protein 4) and STRA6 (stimulated by retinoic acid 6) in pediatric obese subjects with contradictory results.MethodsAn observational study was conducted in the Pediatric and Endocrinology Departments, Targu-Mures, Romania, including 213 children between 5–17 years of age, divided into two groups according to body mass index (BMI) standard deviation score (SDS): case (overweight or obese) and control (normal SDS). Age, sex, basic anthropometric and biochemical measurements and genotype of rs3758539, and rs10882280 for RBP4 gene and rs974456 and rs351224 of STRA6 gene were analyzed. Statistical analysis used SPSS v. 25.0, with a level of significance α = 0.05.ResultsThere is no association between the two gene’s polymorphisms and obesity in our pediatric population. In regression analysis, with HOMA IR (homeostatic model assessment of insulin resistance) as the outcome, the plasmatic level of RBP4 and fat mass percentage are significant predictors, with the model explaining 42% of the HOMA variability. Hypercholesterolemia was significantly associated with male sex, carrying variant allele and heterozygote status of rs10882280 RBP4 gene and wild-type allele rs351224 of STRA6 gene.ConclusionThere is no significant association between obesity and SNPs of the RBP4 and STRA6 in our population, but they seem to play a role in insulin resistance and hypercholesterolemia.

Retinol-binding protein-4 was associated with sensitization to inhalant allergens in the elderly population.

Background/AimsRecent evidence suggests an association between allergic sensitization and metabolic markers. However, this association has rarely been examined in the elderly. Retinol-binding protein-4 (RBP-4) is a recently identified adipokine that acts on the muscle and liver affecting insulin sensitivity. We evaluated the association between metabolic parameters and allergic sensitization in the elderly.MethodsWe analysed the database of the Korean Longitudinal Study on Health and Aging cohort study conducted during 2005 to 2006. Atopy was identified by inhalant allergen skin prick test. Metabolic conditions were assessed using anthropometric indices and serum biomarkers such as fasting glucose, lipid, adiponectin, and RBP-4.ResultsAmong the 854 elderly subjects, 17.2% had atopy. Plasma RBP-4 levels were significantly higher in the atopic elderly than nonatopic elderly (p = 0.003). When RBP-4 percentiles were categorized as under three groups, the prevalence of atopy and current rhinitis increased significantly with percentiles of RBP-4 levels (p = 0.019 and p = 0.007, respectively). Log RBP-4 was associated with atopy (odds ratio [OR], 4.10; p = 0.009) and current rhinitis (OR, 2.73; p = 0.014), but not with current asthma (OR, 1.17; p = 0.824). Higher RBP-4 level in atopic elderly was also observed in current rhinitis patients. Atopy, but not current rhinitis, showed significant relationships with log RBP-4 levels in multivariate analyses adjusted for other metabolic markers including body mass index.ConclusionsRBP-4 positively associated with atopy in the general elderly population irrespective of other metabolic markers.

Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities.

Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol (1) delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analogue (±)-44 possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding.

Novel adipokine associated with OA: retinol binding protein 4 (RBP4) is produced by cartilage and is correlated with MMPs in osteoarthritis patients

ObjectiveRetinol binding protein 4 (RBP4) is a member of the lipocalin family and a vitamin A carrier in the blood. More recently, RBP4 has been described as an adipokine that is involved in insulin resistance and metabolic syndrome (MetS). As obesity, MetS and some adipokines contribute to the pathogenesis of osteoarthritis (OA), we investigated RBP4 in patients with OA.Materials and methodsCartilage, synovial fluid and blood samples were collected from 100 OA patients undergoing total knee replacement surgery. Primary chondrocytes and cartilage tissue were cultured to measure the RBP4 expression. The concentrations of RBP4, other adipokines (adipsin, adiponectin, leptin and resistin) and biomarkers of OA (COMP, MMP-1, MMP-3 and YKL-40) were measured by immunoassay, and gene expression was measured by next-generation RNA sequencing.ResultsThe OA cartilage samples released RBP4 into the culture medium, and the levels correlated positively with the expression of the adipokines adipsin, adiponectin, leptin and resistin. RBP4 was the most prominently expressed of these adipokines in the OA chondrocytes, and the expression of the RBP4 receptors STRA6 (stimulated by retinoic acid gene homologue 6) and TLR4 (Toll-like receptor 4) was also detected. Within the cartilage culture medium, RBP4 showed a positive correlation with MMP-1, MMP-3 and YKL-40. RBP4 was also present in the synovial fluid from the OA patients and correlated positively with the concentrations of RBP4 found in the plasma and the cartilage culture medium. Plasma RBP4 concentrations also showed a positive correlation with MMP-3 and adipsin.ConclusionsWe show here, for the first time, that RBP4 is produced within OA joints and that it is associated with increased levels of adipokines and MMPs. The results suggest a role for RBP4 in the pathogenesis of OA and as a possible target for the disease-modifying drugs for the treatment of OA.

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.

Correction to: Plasma retinol-binding protein-4 and tumor necrosis factor-α are reduced in postmenopausal women after combination of different intensities of circuit resistance training and Zataria supplementation

Correction to: Plasma retinol-binding protein-4 and tumor necrosis factor-α are reduced in postmenopausal women after combination of different intensities of circuit resistance training and Zataria supplementation

Plasma Levels of Retinol Binding Protein 4 Relate to Large VLDL and Small LDL Particles in Subjects with and without Type 2 Diabetes.

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

P745Adipokines retinol binding protein 4 and fatty-acid binding protein 4 in left ventricular hypertrophy

Abstract Background and aim Obese individuals have a high risk of developing heart failure independent of concomitant diseases like diabetes mellitus or arterial hypertension. Hormones secreted by adipose tissue, so-called adipokines such as retinol binding protein 4 (RBP4) or fatty-acid binding protein 4 (FABP4), might constitute a link between obesity and cardiomyopathy. RBP4 is known to be associated with left ventricular hypertrophy, whereas FABP 4 has been reported to display anti- as well as pro-hypertrophic properties. Purpose The aim of the present study was to investigate the association of FABP4 and RBP4 with cardiac magnet resonance imaging (MRI) parameters. Methods We investigated plasma FABP4 and plasma RBP4 levels in 210 patients (70% men, mean age 63 years) who underwent an MRI examination and tested whether FAPB4 and RBP4 levels were associated with the following MRI parameters using linear cox regression: left ventricular end-diastolic diameter (LVEDD), interventricular septal (IVS) wall thickness, posterior wall thickness (PWT), relative wall thickness (RWT), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF). An unadjusted model and a model adjusted for age, sex, body mass index, diabetes mellitus, arterial hypertension, smoking, presence of coronary artery disease, and heart rate were used. Results FABP4 levels were associated with higher PWT (p=0.0044, est. = 0.4) and RWT (p=0.0011, est. = 0.02). The associations were significant in the fully adjusted model (for PWT p=0.013, for RWT p=0.0043). We observed a non-linear, U-shaped relationship between FABP4 and LVEDD, RVEDD, and LVMI. FABP4 levels below the median were associated with lower LVEDD (p=0.0239, est. = −2.7), RVEDD (p=0.0127, est. = −3.3) and LVMI (p&lt;0.001, est. = −7.9). The association were significant in the fully adjusted model for LVMI only (p=0.0016). The associations between FABP4 levels above the median and LVEDD, RVEDD, and LVMI tended to be positive but were not statistically significant. In the unadjusted model, RBP4 was associated with higher IVS (p=0.005, est. = 0.59), PWT (p=0.0135, est. = 0.37), and RWT (p=0.036, est. = 0.02); these associations were not significant in the fully adjusted model. Interestingly, an interaction was observed between age and RBP4 in the association with IVS (p interaction = 0.01). Higher RBP4 and older age might have a stronger effect on IVS than age and RBP4 alone (see Figure). Conclusion Anti- and pro-hypertrophic associations between FABP4 and left ventricular size have been reported. Our results suggest that the pro- and anti-hypertrophic effects of FABP4 are dependent on FABP4 concentrations: lower FABP4 levels have an anti-hypertrophic effect, whereas higher levels have a pro-hypertrophic effect. RBP4 was associated with parameters of cardiac hypertrophy determined by MRI, suggesting a possible link between obesity and cardiomyopathy in an age dependent manner.

Retinol binding protein 4 abundance in plasma and tissues is related to body fat deposition in cattle

Retinol binding protein 4 (RBP4) facilitates the transport of retinol in the body but is also an adipokine and fatty acid transporter. Our study was aimed at investigating the associations between RBP4 abundance and fat deposition in cattle. Blood samples of 246 crossbred bulls were taken at 8 months of age and at slaughter at 18 months of age for the determination of RBP4, hormone levels, and fatty acid composition. Significant correlations between plasma RBP4 abundance at 8 months of age and carcass traits at 18 months of age were detected (e.g., r = 0.3; P < 0.001 to carcass fat). Furthermore, RBP4 abundances in the plasma and subcutaneous fat were higher (P < 0.05) in bulls with increased fat deposition, whereas the liver RBP4 expression was not (P > 0.05). Retinol binding protein 4 was immunohistochemically localized in or close to adipocytes within muscle and adipose tissue and in liver stellate cells but not in hepatocytes. Overall, our results indicate that increased RBP4 levels were associated with increased fat deposition and altered fatty acid composition, but not with altered glucose tolerance, in crossbred bulls. Moreover, our results suggest that adipose-tissue-derived RBP4 may contribute to the circulating RBP4 level.

A New Estimate of the Glomerular Sieving Coefficient for Retinol-Binding Protein 4 Suggests It Is Not Freely Filtered

A New Estimate of the Glomerular Sieving Coefficient for Retinol-Binding Protein 4 Suggests It Is Not Freely Filtered

Plasma retinol-binding protein-4 and tumor necrosis factor-α are reduced in postmenopausal women after combination of different intensities of circuit resistance training and Zataria supplementation.

Zataria is a plant with anti-inflammatory properties, which has been used for the treatment of many diseases. This study investigated the effect of different intensities of circuit resistance training and Zataria supplementation on plasma retinol-binding protein-4 (RBP-4) and tumor necrosis factor-α (TNF-α) in postmenopausal women. Seventy-two postmenopausal women were divided on randomized order into six groups: Control (McGinley and Bishop in J Appl Physiol 121(6):1290-1305, 2016), Training 35% (T35%), Training 55% (T55%), Zataria (Özgünen et al. in Scand J Med Sci Sports 20:140-147, 2010), Zataria/Training 35% (ZT35%), and Zataria/Training 55% (ZT55%). Resist-ance training program included 12 exercise stations (each: 30 s, intensity: 35% and 55% of 1-RM) for 8 weeks (3 sessions/week). Daily (500 mg) Zataria was used after breakfast by participants in ZG, ZT35%, and ZT55% groups. Blood samples were taken 48 h before and after the first and last sessions of training. After the training period the percentage of body fat decreased significantly (P < 0.001) in all trained groups, whereas muscle mass increased significantly (P < 0.01) only in T55% and ZT55% groups. A significant decrease was observed for RBP-4 values (P < 0.05) after training in all groups except for ZG and CG. Also, RBP-4 was significantly lower (P < 0.05) in all groups as compared to CG at the post-test except for ZG. Moreover, significantly lower values (P < 0.05) were found in T55%, ZT35%, and ZT55% as compared to ZG in post-intervention. TNF-α values decreased significantly (P < 0.05) at the post-test as compared to pre-intervention in ZT35% and ZT55%. Also, TNF-α was significantly lower (P < 0.05) in ZT55% compared to CG and T35% in post-test. The results demonstrate clearly that in postmenopausal women, circuit resistance training both at low and moderate intensities cause a greater reduction in RBP-4 and TNF-α when Zataria is supplemented in the diet during training.