Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats

OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.

Effects of Health Qigong Baduanjin on diabetes related indexes in middle-aged obese women / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of Health Qigong Baduanjin on the related indexes of obese middle aged women with diabetes and to provide new ideas for the intervention treatment of diabetes.@*METHODS@#A total of 40 middle-aged female obese diabetic patients were randomly divided into the control group and the exercise group(=20), the age was(57.2±5.4) years old. Fitness training group performed eight new Baduanjin exercises for 24 weeks of intervention, the control group did not exercise, body weight, waist circumference, body mass index (BMI), waist hip ratio (WHR), fasting blood glucose (FPG), glycosylated hemoglobin (HbAlc), triglyceride(TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) levels and serum retinol binding protein 4(RBP4) index were observed in the two groups.@*RESULTS@#After exercise, the waist, WHR, FPG, TG, HbAlc, HDL and RBP4 levels of the the patients in the experimental group were decreased significantly compared with those of before exercise and those of the patients in the experimental control group before and after exercise (<0.05).@*CONCLUSIONS@#Health Qigong Baduanjin can reduce the blood sugar of obese female patients with diabetes, and has some improvement effect on the body part of obesity and blood lipid indicators.

Machine Learning Models for Genetic Risk Assessment of Infants with Non-syndromic Orofacial Cleft / 基因组蛋白质组与生物信息学报·英文版

The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate (NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies (GWAS) have uncovered dozens of single nucleotide polymorphism (SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants in Han and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations. Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.

The relationship between circulating irisin, retinol binding protein-4, adiponectin and inflammatory mediators in patients with metabolic syndrome

ABSTRACT Objective We wanted to investigate whether there is a relationship between circulating irisin, retinol binding protein-4 (RBP-4), adiponectin and proinflammatory mediators implicated in the development of insulin resistance (IR) in metabolic syndrome (MetS). Subjects and methods In 180 individuals, including controls and patients with MetS, we measured fasting plasma insulin, high sensitivity C-reactive protein (hsCRP), pentraxin-3 (PTX-3), interleukin-33 (IL-33), irisin, RBP-4, and adiponectin using ELISA kits. Results While fasting plasma hsCRP, PTX-3, IL-33, irisin, RBP-4 concentrations were higher, adiponectin levels were lower in patients with MetS than in controls. A correlation analysis revealed that plasma irisin levels were positively associated with MetS components such as waist circumference and waist-hip ratio, low density lipoprotein (LDL) and markers of systemic inflammation such as PTX-3, hsCRP, uric acid, and RBP-4. Adiponectin levels were negatively associated with waist circumference, waist-hip ratio, PTX-3 and LDL. Conclusions Although the precise mechanisms are still unclear, irisin, RBP-4, adiponectin and PTX-3 are hallmarks of the MetS, which is related to low-grade inflammation. It is conceivable that irisin and adiponectin might contribute to the development of MetS and may also represent novel MetS components. Future clinical studies are needed to confirm and extend these data.

Circulating omentin-1 might be associated with metabolic health status in different phenotypes of body size

ABSTRACT Objective Adipokines are mediators of body composition and are involved in obesity complications. This study aimed to assess the association of circulating omentin-1, vaspin, and RBP-4 with body composition indices and metabolic health status (MHS) in different phenotypes of body size. Subjects and methods A total of 350 subjects were included in the current cross-sectional study. Body composition was measured using a body composition analyzer, and serum concentrations of omentin-1, vaspin, and RBP-4 were assessed by ELISA kits. Results Circulating omentin-1 was significantly (OR = 1.81, 95% CI: 1.00-1.91, P = 0.01) and marginally (OR = 1.63, 95%CI: 1.00-1.75, P = 0.06) associated with MHS in the overweight and obese subjects, respectively. But no association was seen between omentin-1 and MHS in normal-weight subjects. Serum levels of vaspin and RBP-4 were not correlated with MHS. Furthermore, a significant positive correlation was observed between circulating omentin-1 and body mass index (BMI) as well as fat percentage (P = 0.02) in the MHS group. Serum vaspin concentrations were not related to body composition components in both groups. In addition, in the MHS group, circulating RBP-4 was positively correlated with fat percentage and fat mass (FM) (p < 0.0001) and was negatively correlated with fat-free mass (FFM) and total body water (TBW) (p < 0.0001). In contrast, in the metabolically unhealthy group, RBP-4 was negatively correlated with fat percentage, FM, and BMI (p < 0.0001) and was positively correlated with FFM and TBW (p < 0.0001). Conclusions This study showed that circulating levels of omentin-1 are useful predictors of metabolic health status in overweight and obese people.

Correlation of retinol binding protein 4 with metabolic indexes of glucose and lipid, bile cholesterol saturation index / 中南大学学报(医学版)

OBJECTIVE@#To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI).
@*METHODS@#A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.
@*RESULTS@#The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both P0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all P<0.05). The partial correlation analysis, which was adjusted by age, showed that the bile RBP4 was positively correlated with body mass index (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813), and the serum RBP4 level was correlated with the HOMA-IR and WC independently (multiple regression equation: Yserum RBP4=2.832XHOMA-IR +0.235XWC-20.128). Multiple regression equations showed that HOMA-IR was the strongest correlation factor with RBP4.
@*CONCLUSION@#RBP4 concentrations in serum and bile in the diabetes group are significantly higher than those in the control group. HOMA-IR, BMI and WC are independently correlated with the level of bile RBP4. HOMA-IR and WC are independently correlated with the serum RBP4 level. HOMA-IR is the strongest correlation factor with RBP4. RBP4 might play an important role in the course of gallstone formation in Type 2 diabetes mellitus.

Effect of piglitazone and metformin on retinol-binding protein-4 and adiponectin in patients with type 2 diabetes mellitus complicated with non-alcohol fatty acid liver diseases / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the effects of piglitazone and metformin on retinol-binding protein-4 (RBP-4) and adiponcetin (APN) in patients with type 2 diabetes mellitus (T2DM) complicated with Non alcohol fatty acid liver disease (NAFLD).</p><p><b>METHODS</b>Totally 60 T2DM patients complicated with NAFLD were equally and randomly divided into pioglitazone group and metform group. The levels of biochemical indicators including body mass index (BMI), glucose hemoglobin A1C (GHbA1C), insulin resistance (HOMA-IR), fasting blood glucose (FBG), fasting insulin (FIns), and serum triglycerides (TG) as well as serum RBP-4 and APN level were measured pre-treatment and 12 weeks after treatments.</p><p><b>RESULTS</b>After 12 weeks of treaments, BMI, FBG, HOMA-IR, GHbA1C, FIns, and TG decreased (all P<0.05) in both piglitazone group and metform group. APN increased (all P<0.05) in both groups. RBP-4 decreased (P<0.05) in piglitazone group. Compare with the metform group, the levels of RBP-4, FIns ,and HOMA-IR decreased and BMI increased in piglitazone group (P<0.05).</p><p><b>CONCLUSION</b>Piglitazone is superior to metoform in decreasing RBP-4 level and HOMA-IR in patients with T2DM complicated with NAFLD.</p>

Retinol binding protein 4 and incident diabetes the Atherosclerosis Risk in Communities Study (ARIC Study) / Proteina carreadora de retinol 4 e diabetes incidente Atherosclerosis Risk in Communities Study (ARIC Study)

Background: Retinol binding protein 4 (RBP4) has been described as a link between impaired glucose uptake in adipocytes and systemic insulin sensitivity. Objective: To determine whether RBP4 fasting levels predict the development of type 2 diabetes. Methods: Using a case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 537 who did not over ~9 years within the population-based Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses permitted statistical inference of the RBP4 – incident diabetes associations to the entire cohort. Results: Women in the highest tertile of RBP4 presented greater risk of developing diabetes (HR = 1.74; 95%CI 1.03 – 2.94) in analyses adjusted for age, ethnicity, study center, parental history of diabetes, hypertension, glomerular filtration rate, body mass index, waist-hip ratio, nonesterified fatty acids, adiponectin, leptin, triglycerides and HDL-C. When additionally adjusted for fasting insulin, this association's significance became borderline (HR = 1.68; 95%CI 1.00 – 2.82). No association between RBP4 levels and incident diabetes was found in men. Conclusion: These findings suggest that RBP4 levels may be directly involved in the pathogenesis of type 2 diabetes in women. .

Introdução: A proteína carreadora de retinol 4 (RBP4) tem sido descrita como elo entre uma menor captura de glicose pelos adipócitos e sensibilidade sistêmica à insulina. Objetivo: Determinar se os níveis de RBP4 em jejum predizem diabetes tipo 2. Método: Em um delineamento de caso-coorte, foram acompanhados 543 indivíduos de meia-idade que desenvolveram diabetes e 537 que não desenvolveram diabetes ao longo de 9 anos no estudo Atherosclerosis Risk in Communities Study (ARIC). Foi realizada análise ponderada de riscos proporcionais de Cox para inferência estatística da associação entre os níveis de RBP4 e diabetes incidente na coorte. Resultados: Mulheres com níveis de RBP4 no terceiro tercil apresentaram maior risco de desenvolver diabetes (HR = 1,74; 95% CI 1,03 – 2,94) em análises ajustadas para idade, etnia, centro, história familiar de diabetes, hipertensão, taxa de filtração glomerular, índice de massa corporal, razão cintura-quadril, níveis de ácidos graxos não esterificados, adiponectina, leptina, triglicerídeos e HDL-C. Quando adicionalmente ajustado para os níveis de insulina de jejum, a significância dessa associação se tornou limítrofe (HR = 1,68; 95% CI 1,00 – 2,82). Nenhuma associação foi observada entre RBP4 e diabetes incidente em homens. Conclusão: Esses achados sugerem que os níveis de RBP4 possam estar diretamente envolvidos na patogênese do diabetes tipo 2 em mulheres. .

High fat diet induced insulin resistance and elevated retinol binding protein 4 in female rats; treatment and protection with Berberis vulgaris extract and vitamin A

This research was conducted to investigate two main aims; the first aim was to find if there is a relationship between insulin resistance [IR] and retinol binding protein 4 [RBP4]. The second aim was to use berberis vulgaris extract and vitamin A as protective and/or curative agents against insulin resistance. IR was developed by feeding the female rats a high fat diet [HFD] for six weeks then treating or protecting them with b. vulgaris extract [0.2 g/Kg body weight] or vitamin A [12.8 Micro g/Kg/day] for two weeks. HFD intake elevated insulin level and RBP4 expression that associated with hyperglycemia and hyperlipidemia. Co-administration of vitamin A and B. vulgaris extracts reduced blood glucose level, insulin, body weight and RBP4 expression before, during and after HFD. Furthermore, vitamin A reduced the blood glucose, triglycerides [TG] and cholesterol levels. IR syndrome associated with the RBP4 alteration that gives high indication about the role of RBP4 expression in the IR progression and development. Furthermore, the treatment with vitamin A and/or b. vulgaris alleviated the IR syndrome through the action on RBP4 and Insulin secretion. On the other hand, vitamin A must be avoided for the predisposed IR and prediabetic patients

Effects of retinol binding protein 4 knockdown on the PI3K/Akt pathways in porcine adipocytes / 生物工程学报

Retinol-binding protein 4 (RBP4) is adipocyte-derived secreted adipokines and elevated RBP4 expression level was closely related to insulin resistance and type II diabetes mellitus. However, the exact mechanisms are unknown. To clarify the mechanism, RBP4 lentivirus particles were packaged to infect porcine preadipocytes. Then porcine preadipocytes were activated by insulin or induced model of insulin resistance. RBP4 interference efficiency and the gene expression of each treatment groups in PI3K/Akt pathways were examined by QRT-PCR and Western blotting. The result shows that RBP4 mRNA and protein expressions were suppressed more than 60% (P < 0.01). Furthermore, no matter under insulin stimulation or insulin resistance, RBP4 knockdown significantly increased the mRNA expressions of AKT2, PI3K, GLUT4 and IRS1 compared with the control. The protein phosphorylate levels of AKT2, PI3K, IRS1 arised, meanwhile enhanced the AKT2, PI3K, GLUT4 total protein expressions. Collectively, knockdown of RBP4 increased the insulin sensitivity through upregulated PI3K/Akt pathways related factors' expression and phosphorylation in porcine adipocytes. This research will provide a new idea to treat insulin resistance related diseases.

Expression of human retinol-binding protein 4 in insect baculovirus system and preparation of its polyclonal antibody / 生物工程学报

To prepare recombinant human retinol binding protein 4 (RBP4) by using the baculovirus expression system and to detect its immunogenicity, the fusion DNA fragment of secretory signal peptide SS64 and human RBP4 gene was subcloned into a baculovirus transfer vector pFastBac-dual(pFBd), and the corresponding recombinant transfer plasmid was transformed into E. coli strain DH10bac, after transposition recombinant shuttle bacmid was screened out. The logarithmic phase Sf9 cells were transfected with the recombinant bacmid and then the recombinant baculovirus containing hRBP4 expression box were generated. After amplification of recombinant baculovirus, the recombinant baculovirus seeds were obtained. To express human RBP4, logarithmic phase Sf9 cells were infected with the virus seeds and SDS-PAGE and Western blotting were used to detect and identify the expression. Finally, to prepare a batch of RBP4 protein, logarithmic phase Sf9 cells in suspension culture were infected with recombinant baculovirus seeds and the supernatant was harvested after 120 hours post-infection for purification. Finally for preparation of polyclonal antibody and evaluation of immunogenicity, the recombinant hRBP4 from insect cells and from E. coli were immunized rabbits. Restriction enzyme digestion and sequencing confirmed that the recombinant baculovirus transfer plasmid was constructed correctly, and subsequently recombinant RBP4-bacmid was generated successfully. SDS-PAGE and Western blotting analysis suggested that human RBP4 protein was highly expressed in Sf9 cells with the molecular weight of approximately 23 kDa. The recombinant RBP4 protein could be secreted into the medium efficiently, and the expression level was calculated amount of 100 mg/L. Finally the rabbit antiserum was harvested after recombinant RBP4 immunization, therein the titer of antiserum against baculovirus recombinant RBP4 is 1:100 000 whereas the titer of antiserum against E. coli recombinant RBP4 is only 1:10 000. Overall, human RBP4 was high efficiently expressed successfully with good antigenicity in baculovirus system, and high affinity antiserum was obtained. A solid foundation was laid for the next step of the preparation of human serum RBP4 detection kit.

Plasma level of RBP4 in patients with coronary heart disease and the effect of hyperinsulinemia / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the change of plasma level of retinol binding protein 4 (RBP4) in patients with coronary heart disease, and to explore the effect of hyperinsulinemia.@*METHODS@#This study was carried out at Xiangya Hospital of Central South University, China, from September 2009 to May 2010. Thirty patients with coronary artery disease (the CAD group) were confirmed by coronary angiography, 29 patients with CAD plus hyperinsulinemia (the CAD+HIns group), and 30 healthy subjects were enrolled as controls (the control group). The peripheral blood sample from the anticubital vein was collected aseptically in all the subjects to measure the RBP4 by enzyme linked immunosorbent-assay (ELISA). The height, weight, body mass index (BMI) the waist-to-hip ratio (WHR), the blood pressure, the fasting plasma glucose (FPG), the fasting insulin (Fins), the 2-hour postprandial inslulin (2hPIns), and the homeostasis model assessment-insulin resistance index (HOMA-IR) was measured. The lipids, high sensitivity C reactive protein (hsCRP), uric acid(UA), free fatty acids (FFA) were all examined.@*RESULTS@#The level of plasma RBP4 in the CAD+HIns group was higher than that in the CAD group and the control group (both P0.05). Correlation analysis showed that the plasma RBP4 level was significantly correlated with BMI, FPG, FIns, 2hPIns, HOMA-IR, TG, HDL-C, UA, and hsCRP (r=0.259, 0.331, 0.582, 0.452, 0.600, 0.236, -0.290, 0.243, 0.231, respectively; all P>0.05). Multiple regression analysis showed that BMI, 2hPIns, and HOMA-IR were the independent factors related to RBP4.@*CONCLUSION@#The plasma level of RBP4 does not increase in the CAD group, but it is high in the CAD +HIns group. RBP4 level is related to BMI, lipids, UA, and other cardiovascular risk factors. BMI, 2hPIns, and HOMA-IR are the independent factors associated with RBP4.

Serum retinol binding protein 4 and bone metabolism in patients with type 2 diabetes / 中南大学学报(医学版)

OBJECTIVE@#To determine the relation between serum concentration of retinol binding protein (RBP) 4 and markers of bone metabolism, bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM).@*METHODS@#A total of 82 patients newly diagnosed with T2DM and 46 subjects with normal glucose tolerance (NGT) enrolled in the cross-sectional study. Subset analyses were performed, dividing subjects on the basis of gender into M-T2DM, F-T2DM, M-NGT, and F-NGT. The serum concentrions of RBP4, osteocalcin (OC) and C-terminal telopeptide of collagen type I (CTX) were measured with ELISA. The BMD was measured by dual-energy X-ray absorptiometry (DXA) with a Hologic QDR4500A device.@*RESULTS@#In both the T2DM groups, lnRBP4 showed a positive relationship with lnCTX (M-T2DM, r=0.564, P<0.01; F-T2DM, r=0.386, P=0.018), but no association with lnOC. After adjusting for age, smoking, creatinine clearance rate (CCr), and waist-to-hip ratio (WHR), lnRBP4 still showed a strong association with lnCTX in the M-T2DM group (r'=0.536, P<0.01), but not in F-T2DM (r'=0.317, P=0.072). In the NGT group, there was no relation between lnRBP4 and lnCTX or lnOC. LnRBP4 showed no association with BMD in all groups.@*CONCLUSION@#The level of serum RBP4 may be correlated with the bone metabolism in patients with T2DM.

Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

BACKGROUND/AIMS: Adipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH). The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP), and retinol-binding protein-4 (RBP-4) in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH. METHODS: Polymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps. RESULTS: Patients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively). Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05). CONCLUSIONS: NASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

Serum Retinol-Binding Protein-4 Levels Are Increased in HIV-Infected Subjects with Metabolic Syndrome Receiving Highly Active Antiretroviral Therapy

Metabolic syndrome is an important long term complication in chronic asymptomatic HIV-infected subjects under highly active antiretroviral therapy (HAART), because it can contribute to morbidity and mortality via cardiovascular disease (CVD). Therefore, a predictive marker for early detection of metabolic syndrome may be necessary to prevent CVD in HIV-infected subjects. Retinol-binding protein-4 (RBP-4) has been shown to be associated with metabolic syndrome in various non-HIV-infected populations. We performed a cross-sectional study to evaluate whether serum RBP-4 levels are correlated with metabolic syndrome in HIV-infected subjects receiving HAART. In total, 98 HIV-infected Koreans who had been receiving HAART for at least 6 months were prospectively enrolled. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III criteria, and serum RBP-4 concentrations were measured using human RBP-4 sandwich enzyme-linked immunosorbent assay. Serum RBP-4 levels were significantly higher in HIV-infected subjects receiving HAART with metabolic syndrome (n=33, 33.9+/-7.7 microg/mL) than in those without it (n=65, 29.9+/-7.2 microg/mL) (p=0.012). In multivariate linear regression analysis, the number of components of metabolic syndrome presented and waist circumference were independently, significantly correlated with RBP-4 (p=0.018 and 0.030, respectively). In conclusion, we revealed a strong correlation between RBP-4 and the number of components of metabolic syndrome in HIV-infected subjects receiving HAART.

Serum retinol binding protein 4 is not decreased in congenital generalized lipodystrophy: a case series / Os níveis plasmáticos da retinol binding protein 4 (rbP4) não estão reduzidos na lipodistrofia congênita generalizada: uma série de casos

INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

INTRODUÇÃO: Estudos prévios sugeriram que os níveis plasmáticos da retinol binding protein (RBP4), uma proteína do tecido adiposo, estão associados com a resistência à insulina (RI). A lipodistrofia congênita generalizada (LCG) é uma doença rara caracterizada por ausência de tecido adiposo e RI. O objetivo é determinar os níveis de RBP4 em pacientes com LCG. SUJEITOS E MÉTODOS: Seis (6) pacientes com LCG e um grupo controle saudável foram selecionados para participar no estudo. As variáveis antropométricas e bioquímicas foram comparadas quando comparados os grupos. RESULTADOS: Nenhuma diferença foi observada entre os níveis de RBP4 log entre os grupos (LCG 42,5 [12,5 - 127] vs. controle 57,4 [15,9 - 165]; p = 0,78). Por outro lado, os níveis de leptina foram menores em pacientes com LCG (LCG 0,65 [0,2 - 0,7] vs. controle 10.9 [0,9 - 38,6]; p = 0,015). Nenhuma correlação foi encontrada entre RBP4 e cintura (r = 0,18, p = 0,57) ou IMC (r = 0,24, p = 0,45). CONCLUSÃO: RBP4 não está diminuída na LCG. Esses resultados sugerem que o tecido adiposo pode não ser a principal fonte de RBP4.

Discovery of the serum biomarker proteins in severe preeclampsia by proteomic analysis

Preeclapsia (PE) is a severe disorder that occurs during pregnancy, leading to maternal and fetal morbidity and mortality. PE affects about 3-8% of all pregnancies. In this study, we conducted liquid chromatographymass spectrometry/mass spectrometry (LC-MS/MS) to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with < 1% false discovery rate from the two groups of duplicate analysis. The expression levels of those identified proteins were compared semiquantitatively by spectral counting. To further validate the candidate proteins with a quantitative mass spectrometric method, selective reaction monitoring (SRM) and enzyme linked immune assay (ELISA) of serum samples collected from pregnant women with severe PE (n = 8) or normal pregnant women (n = 5) was conducted. alpha2-HS-glycoprotein (AHSG), retinol binding protein 4 (RBP4) and alpha-1-microglobulin/bikunin (AMBP) and Insulin like growth factor binding protein, acid labile subunit (IGFBP-ALS) were confirmed to be differentially expressed in PE using SRM (P < 0.05). Among these proteins, AHSG was verified by ELISA and showed a statistically significant increase in PE samples when compared to controls.

Association of Serum Retinol Binding Protein 4 with Adiposity and Pubertal Development in Korean Children and Adolescents

Retinol binding protein 4 (RBP4) has been postulated to provide a new link between obesity and insulin resistance. We aimed to assess the relationship between serum RBP4 and insulin resistance by investigating serum RBP4 levels in children and adolescents according to degree of obesity and pubertal stage. A total of 103 (30 lean, 39 overweight, 34 obese) were evaluated for serum RBP4, adiponectin, insulin, glucose and lipid profiles. RBP4 levels of obese and overweight groups were higher than those of lean group. RBP4 level was higher in pubertal group than in prepubertal group. RBP4 was positively correlated with age, height, weight, body mass index (BMI), abdominal circumference, systolic blood pressure, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol and triglyceride, and inversely with adiponectin. In the multiple linear regression analysis, RBP4 was found to be independently associated with pubertal stage, BMI and triglyceride but not with HOMA-IR. In conclusion, serum RBP4 level is related with degree of adiposity and pubertal development. The association of RBP4 with insulin resistance is supposed to be secondary to the relation between RBP4 and adipose tissue in children and adolescents.

Vitamina A e diabetes gestacional: [revisão] / Vitamin A and gestational diabetes: [review]

O diabetes mellitus (DM), patologia de caráter crônico e evolutivo, atualmente apresenta configuração de epidemia mundial. O diabetes gestacional, condição associada tanto à resistência à insulina quanto à diminuição da função das células-β, também caracteriza-se pela elevada incidência em diversas populações e grupos étnicos. Recentemente têm sido constatadas fortes evidências para o comprometimento dos níveis de retinol de gestantes com DM em resposta à evolução dessa patologia. Essa condição torna as gestantes diabéticas mais propensas a apresentar estado bioquímico marginal ou deficiente em vitamina A quando comparadas com as de gestação saudável. Dessa maneira, tendo conhecimento sobre o papel fisiológico da vitamina A e as consequências do DM na gestação, esta revisão visa esclarecer o impacto da instalação do DM sobre os níveis de retinol dessas gestantes, bem como, as consequências que o estado de deficiência em vitamina A poderá causar para essas mulheres e para seus lactantes.

Diabetes mellitus (DM) a pathology with chronic evolution, has now acquired a connotation of global epidemic. Gestational diabetes, a condition associated with insulin resistance and decreased β-cells function is also characterized by a high incidence in different populations and ethnic groups. Recently strong evidence has been found for involvement of retinol levels of pregnant women with DM due to the pathology’s evolution. This condition makes these diabetics prone to have a marginal biochemical profile or a vitamin A deficiency when compared to those of healthy pregnant women. Therefore, with an awareness of the physiological role of vitamin A and consequences of diabetes during pregnancy, this review intends to clarify the impact of DM on retinol levels of these pregnant women and the consequences that vitamin A deficiency may cause to these women and their infants.

Association of Plasma Retinol-Binding Protein 4, Adiponectin, and High Molecular Weight Adiponectin with Insulin Resistance in Non-Diabetic Hypertensive Patients

PURPOSE: The aim of this study was to determine whether retinol-binding protein 4 (RBP4), adiponectin and high molecular weight (HMW) adiponectin are associated with insulin resistance (IR) and metabolic parameters in non-diabetic hypertensive patients. Also, we sought to compare the predictive values of these adipocytokines for IR in non-diabetic hypertensive patients. MATERIALS AND METHODS: Analyses of RBP4, adiponectin, and HMW adiponectin were performed on 308 non-diabetic hypertensives (148 males, age 58 +/- 10 years, 189 non-metabolic syndrome and 119 metabolic syndrome). The homeostasis model assessment (HOMA) index for IR, lipid profiles, and anthropometric measure-ments were assessed. RESULTS: There was no significant difference in RBP4 levels according to the presence of metabolic syndrome, although adiponectin and HMW adiponectin were significantly lower in metabolic syndrome. Correlation analysis of log RBP4 with IR and metabolic indices revealed that there was no significant correlation of RBP4 with waist circumference (r = 0.056, p = 0.324), HDL cholesterol (r = 0.005, p = 0.934), ApoB/ApoAI ratio (r = 0.066, p = 0.270), and the HOMA index (r = 0.017, p = 0.756). However, adiponectin and HMW adiponectin showed significant correlations with the HOMA index (r = - 0.247, p or = 2.5, HMW adiponectin did not demonstrate a superior predictive value for IR compared to adiponectin (AUC = 0.680 vs. 0.648, p = 0.083). The predictive value of RBP4 for IR was minimal (AUC = 0.534). CONCLUSION: RBP4 was not associated with IR or metabolic indices and the predictive value for IR was minimal in hypertensives. HMW adiponectin didn't have a superior predictive value for IR compared to adiponectin. Therefore, we can suggest that RBP4 and HMW adiponectin don't have more additive information than adiponectin in non-diabetic hypertensives.