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.

Expression and its clinical significance of RBP4 in vitreous in patients with proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the concentration of RBP4 and IL-6 in vitreous of proliferative diabetic retinopathy (PDR). METHODS: A total of 65 patients (66 eyes) were enrolled in Department of Ophthalmology, Renmin Hospital of Wuhan University from February 2017 to July 2017 with the informed consent. The patients were divided into PDR group (23 cases) and NPDR group (16 cases). Twenty- six patients without diabetic mellitus (DM) served as control group. The demography was matched among the groups, but the course of DM, the blood glucose level and the HbA1c level were elevated in the PDR group and the NPDR group (all P<0.05). Vitreous samples were collected during the procedure of vitrectomy. RBP4,IL-6,TNF-α concentrations in vitreous specimens were detected by ELISA. The differences of vitreous RBP4, IL-6 and TNF-α in various groups were statistically analyzed by ANOVA, respectively. The correlations between RBP4 and IL - 6, TNF - α were calculated by Pearson correlation analysis. RESULTS:The concentration of RBP4 in PDR group,the NPDR group and control group were 13.68士2.66, 11 03士1 12,10.45士1.17μ g/Ml, and the concentration of IL-6 were 56.0士10.27, 20.92士5.77, 10.26士1.91pg/Ml. RBP4 and IL- 6 concentrations were elevated in PDR group compared with NPDR group and control group, with significant difference among three groups (F = 12. 135, 161.167; P < 0. 01). IL - 6 concentrations in vitreous increased in the NPDR group in comparison with control group(P<0.05). RBP4 concentrations had no significant difference between the NPDR group and the group(P>0 05). Pearson correlation coefficient was significant positive between RBP4 concentration and IL - 6 concentration(r=0.606,P=0.001). CONCLUSION: RBP4 is probability involved in the inflammation pathogenesis of PDR. These results indicate that RBP4 could be a new target for the diagnosis and treatment of PDR.

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.

Expression of Nesfatin -1,RBP4 in maternal blood and umbilical cord blood of gestational diabetes macrosomia and its clinical significance / 中国基层医药

Objective To study the relationship of Nesfatin -1,RBP4 with gestational diabetes mellitus (GDM)and macrosomia,and its clinical significance.Methods 40 patients with GDM were selected as the study subjects,15 cases of newborn children were huge (huge child group),25 cases of neonatal were normal children (normal weight children group).40 cases of normal glucose metabolism (NGT)patients at the same period were selected as the control group.Nesfatin -1,RBP4 levels in maternal blood and umbilical blood were detected by ELISA.Results In the huge child group,the Nesfatin -1 levels in maternal blood and umbilical cord blood were positively correlated (r =0.389,P =0.042),the RBP4 levels in maternal blood and umbilical cord blood were positively correlated(r =0.402,P =0.037).In the huge child group,the Nesfatin -1 levels in maternal blood and blood glucose levels were negatively correlated (r =-0.416,P =0.012),the RBP4 levels in maternal blood and blood glucose levels were positively correlated(r =-0.391,P =0.022).Conclusion Nesfatin -1,RBP4 in GDM and maternal blood and umbilical cord blood of huge children have abnormal expression,and Nesfatin -1,RBP4 levels are closely related to the incidence of GDMand huge children,and Nesfatin -1,RBP4 are important morbidity factors of GDMand huge children.

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 plasma retinol-binding protein 4 levels as risk factor of Type 2 Diabetes Mellitus in abdominal obesity / Journal of the ASEAN Federation of Endocrine Societies

Background@#Abdominal obesity is a risk factor for cardiovascular disease and type 2 diabetes mellitus (T2DM). Plasma retinol-binding protein 4 (RBP4) levels have been reported to increase in the abdominally obese subjects and it has been hypothesized that high plasma protein levels were considered to play an important role in the occurrence of T2DM. @*Objective@#We assessed the value of high plasma RBP4 levels as risk factor of T2DM in abdominally obese subjects. @*Methodology@#A case-control study, nested within a cross-sectional study, on 81 abdominally obese subjects was performed. We studied 33 patients with T2DM, compared with 33 matched controls. The plasma RBP4 levels were measured by ELISA. Insulin resistance (IR) status of the patients were determined using HOMA-IR; β-cell function was determined using HOMA-B. Analysis of variance (ANOVA) was used to test the equality of continuous variables. Forward conditional logistic regression analyses were performed to examine the odds ratios (OR) between high plasma RBP4 levels and consequent T2DM. Path analyses models were performed to assess the influence of risk factors on occurrence of T2DM. @*Result@#Plasma RBP4 levels were significantly increased, while HOMA-B was significantly lower in cases with respect to controls. In analyses adjusted for multiple T2DM risk factors, we observed positive association with high plasma RBP4 levels 9.74 (CI 95%; 2.03 – 46.67) (p = 0.004). It has been proven that high RBP4 level was a dominant risk factor (66.9%, p = < 0.001) influencing incidence of T2DM in the abdominally obese subjects.@*Conclusion@#The present study confirmed that high plasma RBP4 level is associated with increased incident T2DM in the abdominally obese subjects, and suggested that RBP4 has a major effect in the development of T2DM.

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.

The Relationship Between Retinol/Retinol Binding Protein 4 ratio, resistin and inflammation in non diabetic obese Indonesian men.

Aim To verify the correlation between Retinol/RBP4 Ratio, and resistin with inflammation (represented by hsCRP) in non-diabetic obese Indonesian men Methods This was a cross sectional study using 125 subjects. Measured parameters were retinol, RBP4, resistin, and hsCRP. Correlation between retinol, RBP4, resistin, hsCRP and Retinol/RBP4 Ratio was calculated. Cut off point of hsCRP were classiied as follows: <1 mg/l for low risk of inflammation, 1-3 mg/l for moderate risk, and 3-10 mg/l for high risk (according to CVD risk). The Retinol/RBP4 ratio was dichotomized into high (>0.9) and low ratio (≤0.9). The cross tabulation test was performed to predict the inflammation trends described by Retinol/RBP4 Ratio and resistin. Results Retinol was found strongly correlated with RBP4 and resistin (r=0.53; p<0.01). A positive but not significant correlation was found between resistin and Retinol/RBP4 Ratio with hsCRP. In high ratio group, 17.6% subjects were found with low risk inflammation, 26.4% with moderate risk, and 20.8% with high risk, in low ratio group, 8% subjects were low risk inflammation, 20% moderate risk, and 7.2% high risk. Combination between ratio and resistin showed that in “high ratio and low resistin” group, 12% subjects have low risk of inflammation and 8% have high risk. Meanwhile in “low ratio and high resistin” group, 3.2% subjects were found having low risk and 13.6% high risk of inflammation. Conclusions Combination between Retinol/RBP4 Ratio and resistin showed better description about the inflammation risk in non-diabetic obese subjects compare to the ratio itself.

The tumor necrosis factor-?inhibits retinol binding protein 4 secretion in mature 3T3-L1 adipocytes / 重庆医科大学学报

Objective:To explore the effects of tumor necrosis factor-?(TNF-?) on retinol binding protein 4 (RBP4) secreted by mature 3T3-L1 adipocytes in-vitro.Methods:3T3-L1 preadipocytes were cultured and differentiated into the mature adipocytes after 2 days of confluenence.Recombinant TNF-?at different concentrations was added to the culture medium of fully differentiated adipocytes.Total protein of RBP4 secreted by these adipocytes was evaluated by radioimmunoassay(RIA) at various times.Results:(1)Treatment of mature 3T3-L1 adipocytes with TNF-?at different concentrations (0.2,1.0,5.0, 10ng/ml) decreased RBP4 secretion.The inhibitive effect of TNF-?on RBP4 was in dose dependent manner.The level of RBP4 decreased along with the elevated TNF-?concentration in the culture medium.(2)Almost the RBP4 secretion in all experiment groups had a decreasing tread at different time points,but there was no statistical difference in each group.(3) Regression analysis indicated TNF-?had significant associations with RBP4.Conclusion:TNF-?inhibits mature adipocytes RBP4 secretion in-vitro in dose-response effects,but there is no time-response effects.