Serum retinol-binding protein 4 concentrations in response to short-term overfeeding in normal-weight, overweight, and obese men (original) (raw)

Retinol-Binding Protein 4 in Young Men With Low Versus Normal Birth Weight: Physiological Response to Short-Term Overfeeding

Obesity, 2011

Retinol-binding protein 4 (RBP4) is a plasma protein which is elevated in obesity and type 2 diabetes. We aimed to investigate whether RBP4 represents a mechanism underlying the associations between low birth weight (LBW), high-fat diet, and insulin resistance. Forty-six young, lean men with low (n = 20) or normal (n = 26) birth weight underwent a 5-day high-fat high-calorie (HFHC) dietary intervention. In vivo glucose metabolism was assessed by euglycemic-hyperinsulinemic clamp, glucose tracer and intravenous glucose tolerance test techniques. Body composition was measured by a dual-energy x-ray absorptiometry scan, and plasma RBP4 by an enzyme-linked immunosorbent assay. RBP4 was not associated with birth weight, but with BMI (β = 0.9 µg/ml (0.08;1.8) (95% confidence interval), P = 0.03) and plasma levels of low-density lipoprotein cholesterol (β = 5.3 µg/ml (1.9;8.7), P = 0.03) and triglycerides (β = 15.4 µg/ml (9.5;21.3), P < 0.001). Under baseline diet conditions, RBP4 was associated with decreased disposition index (Di) (β = −2.4% (−4.5%;−0.2%), P = 0.04) and increased basal hepatic glucose production rate (HGP) (β = 0.02 mg kg−1 min−1 (0.002;0.04), P = 0.03), but not associated with peripheral glucose disposal rate or hepatic insulin resistance index. RBP4 levels were not influenced by overfeeding or related to peripheral and hepatic insulin resistance provoked by the dietary intervention. In conclusion, plasma RBP4 in young men associates with components of the metabolic syndrome, but is not determined by birth weight and seems not to be involved in short-term high-fat diet-induced insulin resistance.

Retinol-Binding Protein 4 in Human Obesity

Diabetes, 2006

Studies in mice suggest that adipocytes serve as glucose sensors and regulate systemic glucose metabolism through release of serum retinol-binding protein 4 (RBP4). This model has not been validated in humans. RBP4 was highly expressed in isolated mature human adipocytes and secreted by differentiating human adipocytes. In contrast to the animal data, RBP4 mRNA was downregulated in subcutaneous adipose tissue of obese women, and circulating RBP4 concentrations were similar in normal weight, overweight, and obese women (n = 74). RBP4 was positively correlated with GLUT4 expression in adipose tissue, independent of any obesity-associated variable. Five percent weight loss slightly decreased adipose RBP4 expression but did not influence circulating RBP4. In another set of experiments, we stratified patients (n = 14) by low or high basal fasting interstitial glucose concentrations, as determined by the microdialysis technique. Venous glucose concentrations were similar throughout oral g...

Serum levels of retinol binding protein 4 in women with different levels of adiposity and glucose tolerance

Arquivos Brasileiros de Endocrinologia & Metabologia, 2014

Objective Retinol-binding protein 4 (RBP4) is an adipokine responsible for vitamin A (retinol) transportation. Studies associated RBP4 increased levels with severity of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). The study aimed to quantify RBP4 serum standards in women with a wide range of body mass index (BMI) and glucose tolerance level. Subjects and methods: Cross-sectional study was performed with 139 women divided into three groups: Group 1 (lean-control, n = 45) and Group 2 (obese, n = 53) with normal glucose tolerance and group 3 (obese with T2DM, n = 41), called G1, G2 and G3. Were assessed clinical, biochemical, anthropometric and body composition parameters. Results According to data analysis, we obtained in G1 higher RBP4 levels (104.8 ± 76.8 ng/mL) when compared to G2 (87.9 ± 38 ng/mL) and G3 (72.2 ± 15.6 ng/mL) levels. Also, were found: in G1 positive correlations of RBP4 with BMI (r = 0.253), glycated hemoglobin (r = 0.378) and fasting insulin (r = 0....

Retinol-binding protein 4 in obesity

2020

Although many preventive and treatment approaches have been proposed, cardiovascular disease (CVD) remains one of the leading causes of deaths worldwide. Current epidemiological data require the specification of new causative factors, as well as the development of improved diagnostic tools to provide better cardiovascular management. Excessive accumulation of adipose tissue among patients suffering from obesity not only constitutes one of the main risk factors of CVD development but also alters adipokines. Increased attention is devoted to bioactive adipokines, which are also produced by the adipose tissue. The retinol-binding protein 4 (RBP4) has been associated with numerous CVDs and is presumably associated with an increased cardiovascular risk. With this in mind, exploring the role of RBP4, particularly among patients with obesity, could be a promising direction and could lead to better CVD prevention and management in this patient group.

Retinol-binding protein 4 and hyperinsulinemia: The link between obesity and cardiovascular disease

Timocki medicinski glasnik

Kardiovaskularne bolesti (KVB) su vodeći uzrok smrtnosti u svetu, a gojaznost predstavlja jedan od glavnih faktora rizika za ove bolesti. Poremećena sekrecija adipokina [npr., visoke koncentracije retinol-vezujućeg proteina 4 (RBP4), rezistina, leptina, a niske koncentracije adiponektina], inflamacija niskog stepena, kao i povećana produkcija reaktivnih vrsta kiseonika, dovode do poremećaja niza signalnih puteva, insulinske rezistencije (IR), kao i KVB. RBP4 je skoro otkriven adipokin za koji se pretpostavlja da je usko povezan sa IR. Uprkos oprečnim rezultatima brojnih studija, pretpostavlja se da je ovaj protein značajan kardiometabolički faktor rizika, čije visoke koncentracije dovode do nastanka metaboličkog sindroma, tipa 2 dijabetesa i KVB. Bolje poznavanje patofizioloških mehanizama koji dovode do povećanja RBP4 i insulina u krvi mogu dovesti do pronalaska adekvatne terapeutske strategije u cilju smanjenja kardiovaskularnog rizika, pa samim tim i bolesti srca i krvnih sudova kod osoba sa viškom telesne mase. Ključne reči: kardiovaskularne bolesti, retinol-vezujući protein 4, insulinska rezistencija, gojaznost. Summary: Cardiovascular disease (CVD) is the leading cause of death in the world and obesity is one of the main risk factors. Irregular secretion of adipokines [e.g. high retinol binding protein 4 (RBP4), resistin, leptin, respectively, but low adiponectin], low-grade inflammation, as well as an increased production of reactive oxygen species, may lead to impaired insulin signalling, insulin resistance (IR) and CVD. RBP4 is a recently discovered adipokine which is supposed to be closely related to IR. Despite contradictory results obtained from a large number of studies, it is assumed to be a significant cardiometabolic risk factor, leading to metabolic syndrome, type 2 diabetes and CVD development. Better understanding of the patophysiological mechanisms of increased RBP4 and hyperinsulinemia in circulation may lead to a discovery of new target therapy in prevention of CVD, especially in those people who are overweight/obese.

High Circulating Retinol-Binding Protein 4 Is Associated With Elevated Liver Fat but Not With Total, Subcutaneous, Visceral, or Intramyocellular Fat in Humans

Diabetes Care, 2007

OBJECTIVE-Retinol-binding protein 4 (RBP4) is an adipokine that induced insulin resistance in mice, and high plasma RBP4 levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured circulating RBP4 in 75 healthy subjects and used state-of-the-art measurements of body fat distribution. RESEARCH DESIGN AND METHODS-Total body, visceral, and subcutaneous abdominal fat were determined by magnetic resonance tomography and liver fat and intramyocellular fat by localized proton magnetic resonance spectroscopy. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp and, together with insulin clearance, estimated from the oral glucose tolerance test (OGTT). RESULTS-Adjusted circulating RBP4 correlated negatively with insulin sensitivity (clamp: r ϭ Ϫ0.33, P ϭ 0.005; OGTT: r ϭ Ϫ0.36, P ϭ 0.002) and positively with parameters in the fasting state as insulin levels (r ϭ 0.35, P ϭ 0.003) and homeostasis model assessment of insulin resistance (r ϭ 0.34, P ϭ 0.004). In addition, circulating RBP4 correlated negatively with hepatic insulin clearance (r ϭ Ϫ0.25, P ϭ 0.04). Circulating RBP4 was not associated with total body, visceral, or subcutaneous abdominal fat (all P Ն 0.29). Plasma RBP4 levels were also not associated with intramyocellular fat or circulating adiponectin or leptin. In contrast, plasma RBP4 levels correlated positively with liver fat in cross-sectional (r ϭ 0.27, P ϭ 0.03) and longitudinal (r ϭ 0.37, P ϭ 0.04) analyses. CONCLUSIONS-Circulating RBP4 is not associated with the amount of fat in the classical depots or in the ectopic depots in muscle. However, it correlates positively with liver fat. Furthermore, metabolic parameters support the close relationship between circulating RBP4 with liver fat and, presumably, hepatic insulin resistance.

Retinol-binding protein 4 expression in visceral and subcutaneous fat in human obesity

Physiological research / Academia Scientiarum Bohemoslovaca, 2008

Retinol binding protein 4 (RBP4) is a novel adipokine which might be involved in the development of insulin resistance. The aim of the study was to investigate the expression of RBP4 mRNA in subcutaneous and visceral fat depots and the relationship between RBP4 plasma and mRNA levels relative to indices of adiposity and insulin resistance. In 59 Caucasian women (BMI 20 to 49 kg/m(2)) paired samples of subcutaneous and visceral fat were obtained for RBP4, leptin and GLUT 4 mRNA analysis using reverse transcription-quantitative PCR. Euglycemic hyperinsulinemic clamp and computed tomography scans were performed. RBP4 mRNA levels as well as GLUT 4 mRNA and leptin mRNA levels were lower (P<0.001, P<0.01 and P<0.001, respectively) in visceral compared to subcutaneous fat. No differences were found in RBP4 mRNA expression in the two fat depots or in RBP4 plasma levels between subgroups of non-obese subjects (n=26), obese subjects without metabolic syndrome (n=17) and with metaboli...

The High Plasma Retinol Binding Protein 4 Level as a Risk Factor Consequently of Type 2 Diabetes Mellitus of Abdominal Obesity

2011

Abdominal obesity (Ab-Ob) related to cardiometabolic risk, that is riskfactor constellation for succeeded cardiovasculer disease and type 2 DiabetesMellitus (DM). That factors such as atherogenic dislipidemia, hypertension,hyperglycemia, protrombotic state, and proinflammation state. Type 2 DMcharacterised by insulin resistance (IR). Plasma levels of retinol binding protein 4(RBP4) that is secreted by adipocytes are increased in insulin resistance (IR) state.Experiment in mice suggest that elevated RBP4 level cause IR. Although theunderlying mechanism is not clearly understood, RBP4 considered playimportance role consequently of type 2 DM in Ab-Ob.This research was carried out to determine the role of high plasma RBP4level as a risk factor consequently of type 2 DM in Ab-Ob. The research wasconducted by cross sectional analytic in 81 patients with Ab-Ob and case controlstudy with matching on 33 patients with Ab-Ob type 2 DM as cases and 33patients with Ab-Ob non type 2 DM as control...

Association of Serum Retinol Binding Protein 4 with Atherogenic Dyslipidemia in Morbid Obese Patients

PLoS ONE, 2013

Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI.40 kg/m 2) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9614.6; 42.3617.0 and 37.4611.7 mg/ml, respectively) and correlated with triglycerides but not with those of HOMA-IR in the whole population. The multivariate regression model revealed that triglycerides were the strongest predictor of systemic RBP4 levels. Analysis of lipoprotein subfractions in a subpopulation of 80 subjects showed an altered profile of insulin resistant states characterized by higher VLDL, sdLDL and small HDL percentages and lower large HDL percentage. Although RBP4 levels correlated significantly with LDL particle size and small HDL percentage, the latter parameter was independently associated only with RBP4. Our study reveals that systemic RBP4 levels could play an important role in lipid metabolism in morbid obesity, increasing triglyceride levels and contributing to the formation of small HDL.

Is the Retinol-Binding Protein 4 a Possible Risk Factor for Cardiovascular Diseases in Obesity?

International Journal of Molecular Sciences

Although many preventive and treatment approaches have been proposed, cardiovascular disease (CVD) remains one of the leading causes of deaths worldwide. Current epidemiological data require the specification of new causative factors, as well as the development of improved diagnostic tools to provide better cardiovascular management. Excessive accumulation of adipose tissue among patients suffering from obesity not only constitutes one of the main risk factors of CVD development but also alters adipokines. Increased attention is devoted to bioactive adipokines, which are also produced by the adipose tissue. The retinol-binding protein 4 (RBP4) has been associated with numerous CVDs and is presumably associated with an increased cardiovascular risk. With this in mind, exploring the role of RBP4, particularly among patients with obesity, could be a promising direction and could lead to better CVD prevention and management in this patient group. In our review, we summarized the current...