Serum Retinol-binding Protein 4 Research Articles

ITRAQ-based mass spectrometry screen to identify serum biomarkers in systemic lupus erythematosus

ObjectiveSystemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder with no reliable serum biomarkers currently available other than autoantibodies.MethodsIn the present study, isobaric tags for relative and absolute quantitation-based...

Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting.

Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting.

Retinol-binding protein 4 as a promising serum biomarker for the diagnosis and prognosis of hepatocellular Carcinoma

BackgroundThe prognosis of hepatocellular carcinoma (HCC) is universally poor. Early diagnosis plays a pivotal role in determining the outcome of HCC. MethodsWe employed a comparative proteomics approach to identify potential biomarkers and validated the application of retinol-binding protein 4 (RBP4) as a biomarker for HCC. RBP4 protein expression was examined in liver tissues from 80 HCC patients through immunohistochemical analysis. Serum RBP4 concentrations were measured by ELISA in a cohort comprising 290 HCC patients, matched 202 chronic hepatitis B patients and 269 healthy controls. Survival data were collected from HCC patients. The diagnostic and prognostic values of RBP4 were evaluated using receiver operating curve (ROC) analysis. ResultsThe validation results demonstrated a significant reduction in RBP4 levels in both liver tissues and serum samples from HCC patients. ROC analysis of the diagnostic value of RBP4 revealed an AUC of 0.879 (95 % CI: 0.854∼0.903) for HCC. When combined with AFP, the AUC increased to 0.919, with a sensitivity of 87.9 % and specificity of 80 %. Survival analysis revealed significantly reduced overall survival time in individuals with low-expression of RBP4 compared to those with high-expression. The joint prognostic model exhibited an AUC of 0.926 (95 % CI: 0.888∼0.964), which was significantly higher than that of AFP alone (AUC=0.809; P <0.0001). ConclusionsRBP4 shows a great potential as a biomarker with appreciable diagnostic value, complementing the AFP in HCC diagnosis. Additionally, it holds promise as a prognostic biomarker that, when integrated into a combined prognostic model, could greatly improve HCC prognosis efficiency.

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

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

Retinol-Binding Protein 4 and Visfatin Levels in Patients with Periodontitis and Obesity/Overweight: A Systematic Review and Meta-Analysis.

Prior studies demonstrated an equivocal conclusion about the association between the level of retinol-binding protein 4 (RBP4)/visfatin and periodontitis patients with obesity. The aim of our study (Prospero ID: CRD42023469058) was to systematically review the available articles linking the biofluid levels of RBP4/visfatin to the comorbidity of periodontitis and obesity. Clinical trials were screened in accordance with specific inclusion criteria from seven databases up to November 2023. A quality assessment was performed with the Newcastle-Ottawa Scale and ROBINS-I tools for observational and interventional trials, respectively. The standard mean difference (SMD) with a 95% confidence interval (CI) related to the RBP4 level was recorded; the other indicators related to the visfatin level were measured via the mean difference (MD) with the corresponding 95% CI, and Fisher's Z transformation was measured to reveal the association using Review Manager 5.4. The current evidence was based on five observational studies and two interventional studies. All of them were included in the systematic review, and six of them were in the meta-analysis. Statistical analysis indicated that there was no significant difference in the circulating levels of RBP4 in the periodontitis patients with obesity or without, who were labeled as OP or NP, respectively (155 OP-107 NP: SMD = 1.38; 95% CI: -0.18-2.94, p = 0.08), as well as the periodontal healthy patients with a normal weight, who were labelled as NnP (116 OP-79 NnP: SMD = 6.76; 95% CI: -5.34-18.87, p = 0.27). Meanwhile, a significant higher level of serum visfatin was found in the OP patients than that of the NP (86 OP-45 NP: MD = 4.21; 95% CI: 2.65-5.77, p < 0.00001)/NnP (164 OP-88 NnP: MD = 13.02; 95% CI: 7.34-18.70, p < 0.00001) group. In addition, a positive association was observed between the serum RBP4 and body mass index/clinical attachment loss (CAL). And, then, there was a positive association between the serum visfatin and periodontal parameters, including the probing depth, CAL, and plaque index, as well as metabolic parameters, including the total cholesterol, triglycerides, fasting blood glucose, and low-density lipoprotein cholesterol. Here, the circulating RBP4 level was not independently related to the comorbidity of periodontitis and obesity, while serum visfatin was significantly associated with periodontitis and obesity. Notably, the positive association between circulating RBP4/visfatin and the periodontal parameters/metabolic parameters firmly suggested that the higher severity of the obese or periodontal status was associated with an elevated level of serum visfatin or RBP4 in the OP group. With more rigorous longitudinal research, the exact causations between RBP4/visfatin and the patients affected by obesity and periodontitis could be disentangled. RBP4 and visfatin might be novel, enlightening prospective bio-indexes for the targeted treatment of comorbidities.

Are variants of the RBP4 gene associated with serum retinol-binding protein 4 concentrations and carotid intima-media thickness values in women with obesity?

IntroductionSeveral studies showed the correlation of retinol-binding protein 4 (RBP4) with increased cardiovascular risk - including higher values of carotid intima-media thickness (cIMT) - particularly in individuals with obesity. ObjectivesOur study aimed to investigate the impact of rs10882273; rs3758538; rs3758539, and rs7094671 RBP4 gene variants on RBP4 serum concentrations as well as cIMT values (a marker of subclinical atherosclerosis) among female patients with obesity. Patients and methodsWe recruited 74 women with obesity and 24 women without obesity as a study and control group, respectively. The genotypic and allelic frequencies of RBP4 gene variants were evaluated for associations with serum RBP4 and cIMT. ResultsThe median serum RBP4 concentrations were 20.30 µg/mL and 19.80 µg/mL in the patients and control group, respectively (p = 0.740). No significant differences were seen in cIMT values between the two studied groups (0.60 [0.50–1.00] vs. 0.60 ± 0.10 in the patient and control group, respectively); however, the results were close to reaching significance (p = 0.071), similar as in observed association of the minor haplotype AA for rs7084671 and rs375839 with female obesity (p = 0.0559). The correlation analysis showed no significant differences between RBP4 gene variants with serum RBP4 and cIMT. ConclusionsAccording to our knowledge, this is the first study investigating the association between RBP4 gene variants and serum RBP4 and cIMT among Polish female patients with obesity. However, our results show that genetic variants rs10882273, rs3758538, rs3758539, and rs7094671 of the RBP4 gene are not associated with RBP4 serum concentrations or cIMT values among women with obesity.

Effect of non-surgical periodontal treatment on cytokines/adipocytokines levels among periodontitis patients with or without obesity: a systematic review and meta-analysis

BackgroundThe objective of this systematic review and meta-analysis was to evaluate the effects of non-surgical periodontal therapy (NSPT) on inflammatory-related cytokines/adipocytokines in periodontitis patients with or without obesity.MethodsWe followed the preferred reporting items for systematic reviews and meta-analyses statement and registered the study (CRD42022375331) in the Prospective International Register of Systematic Reviews. We screened randomized-controlled trials and controlled clinical trials from six databases up to December 2022. Quality assessment was performed with RoB-2 and ROBINS-I tools for randomized trials and non-randomized trials, respectively. Meta-analysis was carried out using a random-effect model.ResultsWe included seventeen references in the systematic analysis, and sixteen in the meta-analysis. Baseline results of pro-inflammatory biomarkers, including serum interleukin (IL)-6, serum and gingival crevicular fluid (GCF), tumor necrosis factor (TNF)-a, serum C-reactive protein (CRP)/hs-CRP, and serum and GCF resistin, were higher in obesity subjects than in normal weight subjects. The effect of NSPT with respect to levels of cytokines/adipocytokines, including IL-6, TNF-a, CRP/hs-CRP, resistin, adiponectin, leptin and retinol binding protein 4 (RBP4), were then analyzed in the systematic and meta-analysis. After three months of NSPT, serum (MD = -0.54, CI = -0.62 – -0.46), and GCF (MD = -2.70, CI = -4.77 – -0.63) levels of IL-6, along with the serum RBP4 (MD = -0.39, CI = -0.68–0.10) decreased in periodontitis individuals with obesity. NSPT also improved GCF adiponectin levels after three months (MD = 2.37, CI = 0.29 – 4.45) in periodontitis individuals without obesity.ConclusionsObese status altered the baseline levels of cytokines/adipocytokines (serum IL-6, serum and GCF TNF-a, serum CRP/hs-CRP, and serum and GCF resistin). Then NSPT can shift the levels of specific pro-inflammatory mediators and anti-inflammatory mediators in biological fluids, both in obesity and non-obesity individuals. NSPT can reduce serum and GCF IL-6 levels together with serum RBP4 level in individuals with obesity after 3 months, besides, there is no sufficient evidence to prove that obese patients have a statistically significant decrease in the levels of other cytokines compared to patients with normal weight. NSPT can also increase GCF adiponectin level in normal weight individuals after 3 months. Our findings imply the potential ideal follow-up intervals and sensitive biomarkers for clinical bioanalysis in personalized decision-making of effect of NSPT due to patients’ BMI value.

Serum retinol-binding protein 4 in stroke patients: correlation with T helper 17/regulatory T cell imbalance and 3-year cognitive function decline.

Retinol-binding protein 4 (RBP4) promotes atherosclerotic progression and neuronal loss, whereas its association with cognitive impairment in stroke is unclear. Hence, this prospective study aimed to explore the association of serum RBP4 with the T helper (Th)17/regulatory T (Treg) cell ratio and its correlation with cognitive impairment in stroke patients. Peripheral blood samples from 265 stroke patients and 50 healthy controls (HCs) were collected at enrollment for serum RBP4 (by enzyme-linked immunosorbent assay) and Th17 and Treg cells (by flow cytometry) determination. Additionally, stroke patients underwent routine follow-ups, and their Mini-Mental State Examination (MMSE) scores were assessed at baseline and in years 1, 2, and 3 after enrollment. Serum RBP4 was elevated in stroke patients compared to HCs (p < 0.001), with a good ability to differentiate stroke patients from HCs (area under the curve: 0.815). Serum RBP4 was positively associated with Th17 cells (p < 0.001) and the Th17/Treg cell ratio (p < 0.001) and negatively associated with Treg cells (p = 0.003) in stroke patients, whereas it was only positively associated with the Th17/Treg cell ratio (p = 0.027) but not with Th17 (p = 0.075) or Treg (p = 0.130) cells in HCs. Furthermore, increased serum RBP4 was associated with a lower MMSE score (p < 0.001) and a lower incidence of cognition impairment (p = 0.005) at enrollment in stroke patients, as were Th17 cells and the Th17/Treg cell ratio (all p < 0.050). The 1-, 2-, and 3-year MMSE scores in stroke patients were 25.9 ± 2.0, 25.3 ± 2.3, and 24.9 ± 2.3, respectively. More importantly, serum RBP4 was negatively correlated with 1-, 2-, and 3-year MMSE scores (all p < 0.001) and positively associated with 1-year (p = 0.013), 2-year (p = 0.007), and 3-year (p = 0.001) MMSE score declines in stroke patients. Serum RBP4 is positively associated with a Th17/Treg cell imbalance and, more importantly, it is indicative of cognitive function decline within 3 years in stroke patients. Thus, early and timely interventions and physical rehabilitation are more necessary in stroke patients with high serum RBP4.

ОЦЕНКА ЭФФЕКТИВНОСТИ ПРИМЕНЕНИЯ АНАЛОГА ЧЕЛОВЕЧЕСКОГО ГЛЮКАГОНОПОДОБНОГО ПЕПТИДА-1 ЛИРАГЛУТИДА У ПАЦИЕНТОВ С ПОДАГРОЙ И МЕТАБОЛИЧЕСКИ НЕЗДОРОВЫМ ФЕНОТИПОМ ОЖИРЕНИЯ

Introduction. Obesity is a global problem of the XXI century. The most important aspect of metabolic disorders that develop with obesity is a change in the level of serum uric acid (UA) in the blood and the development of gout. Currently, the dynamics of cardiovascular risk factors in patients with obesity on the background of drug therapy is being widely studied. The aim of our study is to study the level of UA, vaspin (VsP), visfatin (VF), omentin (ITLN1), retinol-binding protein-4 (RBP4) in patients with gout and metabolically unhealthy obesity (MNHO) during diet therapy and 3 months of treatment with the drug from the group of human glucagon-like peptide-1 analog (aGLP-1) Liraglutide. Materials and methods: 25 men with gout were examined, the average age was 43.6±7.3 years. Gout was diagnosed according to the classification criteria ACR/EULAR, 2015, Wallace S.L., 1977. Metabolic syndrome was established according to the criteria of GNCA (2013): abdominal obesity - waist circumference ≥ 94 cm in combination with any 2 from the following criteria - an increase in triglycerides (TG) ≥ 1.7 mmol / l; a decrease in high-density lipoproteins (HDL) &lt; 1.0 mmol / l, an increase in low-density lipoproteins (LDL) ≥3.0 mmol / l, blood pressure (BP) ≥ 140/90 mm Hg; increase in plasma glucose ≥ 6.1 mmol / l. At the time of inclusion in the study, all patients had an interictal period of gout. Body mass index (BMI) was calculated using the Quetelet formula: body weight (kg)/height (m²). To assess the type of distribution of adipose tissue, the waist circumference (WT, cm) and hip circumference (HB) were measured with a flexible centimeter tape, with the calculation of the W/H ratio. The concentration of VsP, VF, ITLN1, RBP4 was studied using the enzyme-linked immunosorbent assay method using the kits; the concentration of the level of UA in blood serum and daily urine was studied using the colorimetric method. Liraglutide was injected into the subcutaneous fat of the anterior abdominal wall at a dose of 0.6 mg once a day for the first week. Escalation by 0.6 mg every week was then recommended until a dose of 18 mg per day was reached. Participants then received injections at a dose of 1.8 mg for 3 months. Thus, the observation period was 3 months. Laboratory studies and assessment of anthropometric parameters were carried out initially, as well as after 3 months. The control group consisted of 16 healthy men matched in age. Statistical data processing was carried out using the statistical software package Statistica 13.0. Results. 3 months after treatment, a statistically significant decrease in body weight, BMI and WC was noted (in all cases, p&lt;0.01). Median BMI before treatment was ˗ 38.4 [35.4; 39.2] kg/m², against the background of ongoing therapy - 33.2 [31.4; 34.2] kg/m², and thus the loss of body weight was 23% (p&lt;0.05). Serum UA level decreased by 30.1% (p&lt;0.05) during therapy with a drug from the GLP-1 group. In patients with gout, BMI and regression of obesity were associated with a significant decrease in VsP by 17.2%, VF by 13.8% and RBP4 by 10.4%, and a significant increase in ITLN1 by 12.6%. A direct correlation was established between BMI and WC with the content of VsP, RBP4 and VF in blood serum (correlation coefficients from 0.44 to 0.57, p&lt;0.05) and an inverse correlation with the content of ITLN1 (correlation coefficient -0.29, p&lt;0.05). A direct correlation was found between the serum UA index and the content of VsP, VF, RBP4 (correlation coefficients from 0.31 to 0.49, p&lt;0.05). Conclusion. Patients with gout in combination with MNZO showed a significant increase in serum levels of UA, VsP, RBP4 and VF, against the background of a decrease in the concentration of ITLN1. The use of diet therapy using a drug from the GLP-1 group showed a statistically significant decrease in BMI, WC, serum UA, pro-inflammatory adipokines (VsP, VF and RBP4), and a significant increase in anti-inflammatory cytokines (ITLN1).

The Influence of Thyroid Hormones on Levels of Lipid Profile and Adipokine in Iraqi Women with Thyroid Disorders

Hypothyroidism and hyperthyroidism are prevalent endocrine diseases.These have significant implications for lipid synthesis, mobilization, and metabolism. Retinol-binding protein 4 is a new adipokine implicated in some physiological and pathological processes, such as metabolic and endocrine disorders. Its elevation aids in the diagnosis of thyroid problems. The present study includes 60 women with thyroid diseases; 30 of them have hypothyroidism and 30 have hyperthyroidism. This study includes 20 healthy women as a control group. For each participant anthropometric, biochemical Thyroid-stimulating hormone, triiodothyronine, Thyroxine, lipid profile, and retinol binding protein-4 are measured. The results show that hypothyroid women have significantly higher levels of total cholesterol, triglycerides, and lowdensity lipoprotein cholesterol as compared to the hyperthyroid or control group. The serum of total cholesterol, triglycerides, and low-density lipoprotein cholesterol are significantly lower in hyperthyroid women compared to the hypothyroid or control group. In addition, there are no significant differences in blood high-density lipoprotein cholesterol concentrations among the three groups. Furthermore, serum retinolbinding protein-4 levels were higher in the hyperthyroid group compared to the hypothyroid or control groups. According to the findings of this study, hypothyroidism causes dyslipidemia, which raises the risk of cardiovascular disease while hyperthyroidism causes abnormalities in lipid profiles. Additionally, hyperthyroidism causes an increase in serum retinol-binding protein-4 levels in the blood.

Targeting Retinol-Binding Protein 4 (RBP4) in the Management of Cardiometabolic Diseases.

The ancient use of herbs for the treatment of various human diseases have been documented, with several scientific literatures supporting the use of medicinal plants. There is however a major concern about the phyto-constituents in the plants that performs the healing function and the mechanism by which it works for different ailments are still a research prospect. Cardiometabolic disease (CMD) is no doubt becoming more frequent globally and this is due to poor approach in therapy, contrary effects linked with intensive control, inept strategies with old drugs, inadequate control of some risk factors and lack of knowledge of the pathophysiological mechanisms that lead to this malaise. Retinol-binding protein 4 (RBP4) are predominantly secreted in the liver and adipose tissues and several researches have observed that elevation in serum levels of RBP4 often observed in obese experimental animals and human subjects causes CMD (obesity, insulin resistance, hyperlipidemia, etc.). RBP4 has gained special attention in the last 20years in the field of metabolism research. This review aims to show research interaction of some medicinal plants targeting RBP4 in treating CMD and to encourage researchers, who are interested in CMD drug design, to focus on medicinal plants that inhibit the secretion of serum RBP4 in the adipose tissue for therapeutic approach to CMD. It also aims to identify the major bioactive compounds of plants that serves as a better and cheaper drug candidate for CMD and also study the signaling pathway which the plant material uses to regulate the metabolic consequences.

Retinol-Binding Protein 4 Actives Adipocyte Renin–Angiotensin System via Toll-Like Receptor 4

Abstract Background To investigate the relationship between the levels of serum adipokine retinol-binding protein 4 (RBP4) levels and essential hypertension as well as to explore the role and mechanism of RBP4-induced activation of renin–angiotensin system (RAS) in hypertension in adipocyte. Methods From December 2016 to March 2019, 96 hypertensive patients without treatment and 64 healthy nonhypertensive subjects were recruited. The difference in serum RBP4 levels between the 2 groups was compared, and the relationship between serum RBP4 and hypertension was analyzed by multivariate logistic regression. In mouse primary white adipocytes, the effect and mechanism of RBP4 on RAS in adipocyte were determined by experiment of adenovirus transfected RBP4 overexpression. Protein expression of Toll-like receptor 4 (TLR4) and RAS key components was determined by western blotting. The level of angiotensin II (Ang II) in cell supernatant was measured by enzyme-linked immunosorbent assay. We also observed the effect of TLR4 inhibitor TAK242 on RAS activation induced by RBP4 overexpression. Results Serum RBP4 levels were significantly higher in patients with essential hypertension than in healthy nonhypertensive subjects [30.14 (23.76–40.65) vs. 25.05 (20.05–31.04) µg/ml, P &amp;lt; 0.01]. Multivariate logistic regression analysis showed that RBP4 was independently associated with hypertension [OR 1.10 (95% CI 1.06–1.14), P = 0.002]. In RBP4-transfected adipocytes, the expression of angiotensin-converting enzyme, angiotensinogen, renin/angiotensin-forming enzyme 1, and angiotensin II receptor 1, as well as the level of Ang II in cell supernatant (P &amp;lt; 0.05) were significantly increased. Whereas, activation of RAS system was markedly reduced when RBP4-transfected adipocyte was treated by TAK242 (P &amp;lt; 0.05). Conclusions Serum RBP4 is associated with hypertension. TLR4-mediated activation of RAS might be mechanisms underlying the effects of RBP4 on blood pressure.

Evaluation of maternal serum SERPINC1, E-selectin, P-selectin, RBP4 and PP13 levels in pregnancies complicated with preeclampsia

Objective The aim of this study is to investigate whether Serpin clade C (SERPINC1), E-selectin, P-selectin, Placental protein 13 (PP13), and Retinol-binding protein-4 (RBP4) levels in maternal serum were associated with the presence of preeclampsia and to compare them with uncomplicated pregnancies. Methods This prospective study included 40 women with preeclampsia and 40 healthy pregnant women. An enzyme-linked immunosorbent assay kit was used to measure serum SERPINC1, E-selectin, P-selectin, PP13, and RBP4 levels. Results The preeclampsia group had significantly higher E-selectin and P-selectin levels than the control group. PP13 and SERPINC1 levels were also significantly lower than the control group. There was no significant difference in RBP4 levels. The receiver operating characteristic curve revealed the best cutoff values for the following: E-selectin >19.2 ng/mL, with 87.5% sensitivity and 95% specificity; P-selectin >5.1 ng/mL, with 97.5% sensitivity and 100% specificity; PP13 ≤ 107.03 pg/mL, with 72.5% sensitivity and 77.5% specificity; and SERPINC1 ≤ 87.76 ng/mL, with 100% sensitivity and 97.5% specificity. Conclusion In this study, the endothelial dysfunction parameters SERPINC1, PP13, E-selectin, and P-selectin were found to be associated with preeclampsia. Endothelial dysfunction biomarkers in maternal non-serum body fluids may differ. More research is needed, especially to determine the relationship between SERPINC1 and preeclampsia.

Association of Leptin and Retinol Binding Protein 4 with the Risk of Gestational Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

The positive correlation between serum levels of retinol binding protein 4 (RBP4) and gestational diabetes (GDM) has been proven in the previous meta-analysis on case-control studies. However, its association with serum levels of leptin is not studied in any meta-analysis. Therefore, we performed an updated systematic review of observational studies evaluating the association between serum RBP4 and leptin with the risk of GDM. A systematic search was performed on four databases, including PubMed, Scopus, Web of Science, and Google Scholar, up to March 2021. After screening and deleting duplicates, nine articles met our inclusion criteria. Studies had case-control and cohort design, and included 5074 participants with a mean age range between 18 and 32.65 years (2359 participants for RBP4 and 2715 participants for leptin). Interestingly, this meta-analysis revealed higher levels of RBP4 (OR=2.04; 95% CI: 1.37, 3.04) and leptin (OR=2.32; 95% CI: 1.39, 3.87) are significantly associated with the increased risk of overall GDM. The subgroup analysis approved the results based on the study design, trimester of pregnancy and serum/plasms to investigate the source of heterogeneity. The present meta-analysis determines serum leptin and RBP4 levels as predictors of GDM occurrence. However, studies included in this meta-analysis showed significant heterogeneity.

Elevated retinal retinol-binding protein 4 levels in diabetic mice can induce retinal neurodegeneration through microglia.

Retinol-binding protein 4 (RBP4) is the sole specific transport protein for vitamin A (retinol), but it is also an adipokine with retinol-independent, proinflammatory activity associated with diabetes and diabetic retinopathy (DR). Most previous studies focused on the relationship between elevated serum RBP4 levels and DR. Since serum RBP4 cannot cross the blood-retinal barrier, the level of retinal RBP4 is independent of serum RBP4, and the change of retinal RBP4 and its potential pathogenic mechanism in DR has not been studied. We showed that the retinal RBP4 levels were raised in Streptozotocin-induced diabetic mice though the serum RBP4 levels were decreased. Intravitreal injection of RBP4 protein in mice results in activation of microglia, loss of retinal ganglion cells (RGCs) and bipolar cells. Minocycline (MC) can reverse the activation of microglia induced by RBP4, protecting RGCs and bipolar cells. These findings suggest that retinal RBP4 levels were raised in diabetic mice, and RBP4 can directly induce retinal neurodegeneration in mice through microglia. RESEARCH HIGHLIGHTS: We revealed that the retinal RBP4 levels were raised in diabetes and elevated retinal RBP4 can induce retinal neurodegeneration through microglia. Inhibition of neuroinflammation or reduction of retinal RBP4 level may be a potential therapeutic strategy to prevent diabetic retinal neurodegeration.

Correlation of serum RBP4 level with oxidative stress and unstable carotid plaque in patients with cerebral infarction.

ObjectivesThis study aimed to investigate the changes in serum levels of retinol-binding protein 4 (RBP4) with cerebral infarction, relationship of RBP4 with oxidative stress and carotid atherosclerosis, and its possible role in cerebral infarction.Materials and methodsAccording to the results of cervical vascular ultrasound, the experimental group was divided into three groups: intima thickening group (n = 31), stable plaque group (n = 51), and unstable plaque group (n = 54). Forty healthy subjects were selected as the control group. Their serum levels of RBP4, 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), and catalase (CAT) were measured. Carotid vascular ultrasound was used to measure the plaque area and intima-media thickness (IMT).ResultsThe serum RBP4 and 8-iso-PGF2α levels, IMT and plaque area in the control, intimal thickening, stable plaque, and unstable plaque groups increased, while the serum level of CAT decreased (P < 0.001). The serum levels of RBP4 positively correlated with 8-iso-PGF2α, IMT, and plaque area and negatively correlated with CAT level. The area under the receiver operating characteristic curve was 0.778 in predicting unstable plaques.ConclusionsThe serum levels of RBP4 were significantly elevated in elderly patients with cerebral infarction and correlated with oxidative stress injury and the degree of atherosclerosis. Serum RBP4 has diagnostic value for unstable plaques in carotid arteries.

Serum Levels of CXCL-13, RBP-4, and IL-6, and Correlation Analysis of Patients with Graves' Disease.

Objective To investigate the serum levels of CXC chemokine 13 (CXCL-13), retinol binding protein-4 (RBP-4), and interleukin 6 (IL-6) in patients with Graves' disease (GD). The correlation between CXCL-13, RBP-4, and IL-6 levels and the basal metabolic rate (BMR) was analyzed. Methods 118 GD patients diagnosed in our hospital were selected as the observation group from March 2017 to December 2018. According to the measured BMR value, 118 GD patients were divided into the mild group (n = 39), the moderate group (n = 47), and the severe group (n = 32), three subgroups. 60 healthy subjects were selected as the control group. The serum levels of CXCL-13, RBP-4, IL-6, TSH, FT3, and FT4 in every group were measured. Pearson correlation analysis was used to observe the correlation of serum CXCL-13, RBP-4, and IL-6 levels with TSH, FT3, FT4, and BMR. Results The levels of serum CXCL-13, RBP-4, and IL-6 in the observation group were higher than those of the control group, and the differences were statistically significant (P < 0.05). The levels of serum CXCL-13, RBP-4, and IL-6 in the moderate and severe groups were higher than those in the mild group, and the differences were statistically significant (P < 0.05). The levels of serum CXCL-13, RBP-4, and IL-6 in the severe group were higher than those in the moderate group, and the differences were statistically significant (P < 0.05). Pearson correlation analysis showed that the serum levels of CXCL-13, RBP-4, and IL-6 in GD patients were negatively correlated with TSH levels and positively correlated with FT3 and FT4 levels. Serum CXCL-13, RBP-4, and IL-6 levels in GD patients were positively correlated with BMR (r = 0.915, r = 0.942, r = 0.926, P < 0.001). Conclusion Serum CXCL-13, RBP-4, and IL-6 levels are elevated in patients with GD, and with the aggravation of the disease, the serum CXCL-13, RBP-4, and IL-6 levels also increase, showing a positive correlation, which can be used as indicators to reflect the degree of GD.

Correlation between Retinol Binding Protein 4 and CT Perfusion Imaging and Prognosis in Patients with Acute Ischemic Stroke Based on Cell Imaging Data Analysis.

Objective In order to explore the correlation between the retinol binding protein 4 (RBP4) and prognosis of patients with acute ischemic stroke (AIS), CT perfusion imaging can be used to scan the brain tissue of patients, which can identify abnormal perfusion areas and ischemic penumbra brain tissue, so as to provide a basis for doctors to formulate a reasonable clinical treatment plan. Methods 200 patients with first-episode acute ischemic stroke were selected from the Department of Neurology of our hospital, including 128 males and 72 females, aged between 32 and 85 years, with an average age of 45 ± 4.3 years. After admission, the patients were tested for xanthol binding protein 4 in time, the patient's demographic data and the basic clinical data were recorded, the degree of brain injury was evaluated, and the short-term outcome was evaluated after treatment. Results A total of 200 AIS patients with different degrees of brain injury were included in this study, including 128 males and 78 females, aged between 32 and 85 years, with an average age of 45 ± 4.3 years. Among them, 100 patients used CT perfusion imaging for brain scanning as the observation group, 100 patients used traditional imaging methods as the reference group, and 100 healthy people were included as the blank group. At the same time, the contents of total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured by using an automatic biochemical analyzer. The patients were evaluated in the early stage of treatment and the effect of prognostic intervention was recorded. Conclusion The application of CT perfusion imaging in the adjuvant treatment of AIS patients was helpful to identify the abnormal perfusion area and the brain tissue of ischemic penumbra, so as to provide a basis for doctors' follow-up treatment. At the same time, AIS patients with high serum RBP4 level had mild stroke severity, good short-term prognosis, and improved treatment effect, which improved patients' quality of life.

Serum Retinol Binding Protein 4 as a Potential Biomarker for Sarcopenia in Older Adults.

Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. Retinol-binding protein 4 (RBP4) is an adipokine with pro-inflammatory effects. However, the change of RBP4 concentration and its role in sarcopenia remains unclear. The aim of this study was to evaluate the association of serum RBP4 level with sarcopenia in the older adults. A total of 816 community-dwelling older adults aged ≥60 years were enrolled. Serum RBP4 was measured by enzyme-linked immunosorbent assay. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were measured. We found that serum RBP4 levels were higher in patients with sarcopenia when compared with those without sarcopenias (44.3 [33.9-57.7] vs 38.0 [28.0-48.4] μg/mL). Receiver operating characteristic curve analysis indicated that the optimal cutoff value of serum RBP4 level that predicted sarcopenia was 38.79 μg/mL with a sensitivity of 67.8% and a specificity of 53.3%. Multivariate logistic regression analysis showed that the subjects with a higher level of RBP4 had a higher risk of sarcopenia (adjusted odds ratio [OR] = 2.036, 95% CI = 1.449-2.861). Serum RBP4 concentration was negatively correlated with grip strength (r = -.098), gait speed (r = -.186), and AMSI (r = -.096). Moreover, serum RBP4 levels were higher in patients with severe sarcopenia when compared with those with moderate sarcopenia (49.0 [37.3-61.2] vs 40.4 [31.3-51.2] μg/mL). Taken together, our results demonstrate that serum RBP4 level is correlated with the risk and severity of sarcopenia in the older adults, indicating that RBP4 might serve as a surrogate biomarker for the screening and evaluation of sarcopenia.

Correlation of Blood Glucose and Pancreatic Islet Function with Serum Retinol-Binding Protein 4, Serum Cystatin C, and Human New Satiety Molecule Protein-1 in Pregnant Women with Gestational Diabetes Mellitus.

Objective To investigate the correlation of blood glucose and islet function with serum retinol-binding protein 4, serum cystatin C, and nesfatin-1 levels in women with gestational diabetes mellitus. Methods Between June 2018 and June 2020, 70 patients with gestational diabetes mellitus were included in a study group and 70 healthy pregnant women were recruited into a healthy group. Alterations in fasting blood glucose (FPG), glycated hemoglobin (HbA1c), fasting serum insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), serum retinol-binding protein 4 (RBP4), serum cystatin C (CysC), and nesfatin-1 of all eligible participants were analyzed, and the occurrence of complications was recorded. Correlation analysis of serum RBP4, serum CysC, and nesfatin-1 levels with blood glucose and islet function in women with gestational diabetes mellitus was performed. Results Gestational diabetes mellitus was associated with significantly higher levels of FPG, HbA1c, and HOMA-IR and lower levels of FINS (6.58 ± 1.41, 9.24 ± 1.09, 3.21 ± 2.03, 8.23 ± 2.21) versus a healthy condition (5.23 ± 0.85, 7.61 ± 0.67, 2.42 ± 1.14, 10.54 ± 2.15) (P < 0.05). Women with gestational diabetes mellitus showed significantly higher levels of serum RBP4, serum CysC, and nesfatin-1 (62.45 ± 7.86, 1.95 ± 0.59, 2.65 ± 0.49) versus healthy pregnant women (45.48 ± 6.15, 1.03 ± 0.67, 1.42 ± 0.62) (P < 0.05). With serum RBP4, serum CysC, and nesfatin-1 as dependent variables, univariate correlation analysis showed that serum RBP4, serum CysC, and nesfatin-1 levels were positively correlated with FPG and HbA1c levels and HOMA-IR, and negatively correlated with FINS in women with gestational diabetes mellitus (P < 0.05). Gestational diabetes mellitus resulted in a significantly higher incidence of preterm delivery, cesarean section, excess amniotic fluid, and premature rupture of membranes versus a healthy status (P < 0.05). Conclusion Glucose metabolism and islet function in women with gestational diabetes are significantly correlated with serum RBP4, serum CysC, and nesfatin-1 levels, which shows great potential for the prevention and treatment of gestational diabetes mellitus and perinatal complications.