Serum Retinol-Binding Protein Is More Highly Expressed in Visceral than in Subcutaneous Adipose Tissue and Is a Marker of Intra-abdominal Fat Mass

Klöting, Nora; Graham, Timothy E.; Berndt, Janin; Kralisch, Susan; Kovacs, Peter; Wason, Christopher; Faßhauer, Mathias; Schön, Michael P.; Stümvoll, Michael; Blüher, Matthias; Kahn, Barbara B.

doi:10.1016/j.cmet.2007.06.002

Cited by 365 publications

(335 citation statements)

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“…However, the physiological mechanisms that link fetal growth and adverse outcome remain unknown. RBP4 was found to be secreted by adipocytes and to be up-regulated in adipose tissue and serum of insulin-resistant human beings (17). These findings suggest that RBP4 may play an important role in metabolic homeostasis in insulin-resistant states.…”

Section: Discussionmentioning

confidence: 75%

“…However, the close relationship between RBP4 and birth size measurements as well as the significant difference in RBP4 between SGA and AGA newborns strongly suggest that measured RBP4 was mainly from fetal origin. RBP4 levels have been linked to visceral adiposity, visceral fat representing a major source of RBP4 in conditions associated with IR (17). Data from absorptiometry studies show that the amount of fat mass is strikingly reduced in neonates who suffered intrauterine growth retardation, indicating an altered development of adipose tissue (12).…”

Section: Discussionmentioning

confidence: 99%

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Retinol-binding protein 4 in neonates born small for gestational age

Giacomozzi

Ghirri

Lapolla

et al. 2010

J Endocrinol Invest

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ABSTRACT. Background: Retinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance and Type 2 diabetes. The relationship of RBP4 with insulin resistance and metabolic risk in human beings has been the subject of several studies. Subjects born small for gestational age (SGA) are at risk of insulin resistance and Type 2 diabetes. Though RBP4 could represent an early marker of insulin resistance, to date, none have determined RBP4 in SGA children. Aim: Our aim was to measure RBP4 concentrations in cord blood of SGA newborns compared with those in children born with a birth weight appropriate for gestational age (AGA) and to determine whether serum RBP4 levels at birth correlate with insulin sensitivity markers. Subjects and methods: Sixty-four newborns, 17 born SGA (mean gestational age: 36.4±2.1 weeks), and 47 born AGA (mean gestational age: 37.0±3.6 weeks) were studied. The main outcome measures included anthropometry, lipid profile, insulin, homeostasis model assessment, quantitative insulin-sensitivity check index, adiponectin, and RBP4. Results: RBP4 concentrations were significantly reduced in SGA newborns (p<0.002). No relationship was found between RBP4 and insulin sensitivity parameters. Stepwise regression analysis revealed that birth weight was the major predictor of RBP4 serum concentrations (p<0.001). Conclusion: RBP4 is reduced in SGA newborns, birth weight representing the major determinant of RBP4 concentrations, and is not related to insulin sensitivity. No significant difference in adiponectin levels and insulin sensitivity markers was found between SGA and AGA neonates. INTRODUCTIONRetinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance (IR) and Type 2 diabetes. RBP4 could play a role in obesity-induced IR, since chronic elevation of RBP4 in mice increases hepatic glucose production, down-regulates insulin signaling in muscle, and causes systemic IR (1). Furthermore, lowering elevated serum RBP4 levels in obese mice with a synthetic retinoid improves insulin sensitivity and normalizes glucose tolerance (1). In humans, the link between RBP4 and IR is less clear. In adulthood, serum RBP4 levels have been shown to correlate with the magnitude of IR in subjects with obesity, impaired glucose tolerance, and Type 2 diabetes (2). Moreover, elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body mass index, waist-tohip ratio, serum triglyceride levels, and systolic blood pressure and decreased HDL cholesterol levels (2). In childhood, a relationship between serum RBP4 and obesity and components of the metabolic syndrome has been described in pre-pubertal and early pubertal children (3).Increased risk of developing IR and Type 2 diabetes in adulthood is associated with low birth weight (4). Although this association is clearly established in adults (5), results in children are still conflicting (6). Some authors have sugg...

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Retinol-binding protein 4 in neonates born small for gestational age

Giacomozzi

Ghirri

Lapolla

et al. 2010

J Endocrinol Invest

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“…Moreover, RBP4 serum levels highly correlate with the degree of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes, as well as in nonobese subjects with family history of type 2 diabetes (2). Recently, we found increased RBP4 mRNA expression in visceral compared with subcutaneous adipose tissue and serum RBP4 concentrations correlated with RBP4 mRNA expression, intra-abdominal fat mass, total body fat mass, A1C, and insulin resistance (3).…”

Section: S Erum Retinol Binding Protein 4 (Rbp4) Is a Newmentioning

confidence: 88%

Effects of Genetic Variation in the Human Retinol Binding Protein-4 Gene (RBP4) on Insulin Resistance and Fat Depot–Specific mRNA Expression

Kovacs¹,

Geyer

Berndt³

et al. 2007

Diabetes

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OBJECTIVE-Serum retinol binding protein 4 (RBP4) is a new liver-and adipocyte-derived signal that may contribute to insulin resistance. Therefore, the RBP4 gene represents a plausible candidate gene involved in susceptibility to type 2 diabetes.RESEARCH DESIGN AND METHODS-In this study, the RBP4 gene was sequenced in DNA samples from 48 nonrelated Caucasian subjects. Five novel and three known single nucleotide polymorphisms (SNPs) were identified. Furthermore, five recently reported SNPs were genotyped in 90 subjects. Six SNPs, representative of their linkage disequilibrium groups, were then genotyped in 934 diabetic and 716 nondiabetic subjects. RESULTS-A haplotype of six common SNPs (A-G-G-T-G-C)was significantly increased in 934 case subjects with type 2 diabetes compared with 537 healthy control subjects with normal glucose tolerance (P ϭ 0.02; odds ratio 1.37 [95% CI 1.05-1.79]). Furthermore, in the cohort of 716 nondiabetic Caucasian subjects, carriers of the A-G-G-T-G-C haplotype had significantly higher mean fasting plasma insulin and 2-h plasma glucose than subjects without the haplotype. Two single SNPs (rs10882283 and rs10882273) were also associated with BMI, waist-to-hip ratio, and fasting plasma insulin, and several SNPs were associated with circulating free fatty acids (all adjusted P Ͻ 0.05). In addition, subjects carrying a previously reported diabetes-associated haplotype had significantly higher mRNA levels in visceral adipose tissue (adjusted P Ͻ 0.05) in a subgroup of nondiabetic subjects (n ϭ 170) with measurements of RBP4 mRNA expression in visceral and subcutaneous fat depots. CONCLUSIONS-Our data indicate a role of RBP4 genetic variation in susceptibility to type 2 diabetes and insulin resistance, possibly through an effect on RBP4 expression. Diabetes 56:3095-3100, 2007 S erum retinol binding protein 4 (RBP4) is a new adipocyte-derived signal linking adipose tissue dysfunction to systemic insulin resistance and thereby likely contributing to the pathogenesis of type 2 diabetes. Serum RBP4 is elevated in insulin-resistant mice, as well as in humans, with obesity and type 2 diabetes and can be normalized by insulin-sensitizing drugs (1). Moreover, RBP4 serum levels highly correlate with the degree of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes, as well as in nonobese subjects with family history of type 2 diabetes (2). Recently, we found increased RBP4 mRNA expression in visceral compared with subcutaneous adipose tissue and serum RBP4 concentrations correlated with RBP4 mRNA expression, intra-abdominal fat mass, total body fat mass, A1C, and insulin resistance (3).RBP4 is encoded by the RBP4 gene, which maps to chromosome 10q23-q24, a region that has been linked to increased risk for type 2 diabetes in different populations (4,5). Despite known physiology as well as chromosomal location, to date, very few studies on the effects of genetic variation in the RBP4 gene on increased metabolic risk in humans have been reported (6,7). We therefor...

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“…Mody et al (28) also demonstrated decreased renal clearance and elevated plasma RBP4 levels in ob/ob mice as a result of increased plasma TTR concentrations. Furthermore, higher plasma TTR concentrations were also observed in humans with obesity and/or insulin resistance (16). Increased levels of TTR mRNA and protein have been demonstrated in both pancreatic b-and a-cells during T2D (29)(30)(31)(32).…”

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 2 Diabetesmentioning

confidence: 95%

“…These observations coupled with direct effects of RBP4 demonstrated in animal and cell culture models (5, 13) imply a strong role of RBP4 in obesitymediated insulin resistance. Recently, extensive trials in insulinresistant adults and children from multiple ethnic backgrounds revealed a strong association between plasma RBP4 concentrations with insulin resistance, obesity, and metabolic syndrome components (16)(17)(18)(19)(20). In addition, interventions that ameliorate insulin resistance in humans also reduced plasma RBP4 levels (11,14,(21)(22)(23).…”

Section: Plasma Rbp4 Ttr and Retinol Levels In Type 2 Diabetesmentioning

confidence: 99%

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

et al. 2012

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SummaryRetinol-binding protein 4 (RBP4) is the principle carrier of retinol in the human plasma, which circulates as a complex with transthyretin (TTR), a homotetrameric thyroxine transport protein. Although this complex formation is thought to prevent glomerular filtration of RBP4, it also stabilizes the quaternary structure of TTR. Recent studies indicate elevated plasma levels of RBP4 in type 2 diabetes (T2D). In contrast, reduced RBP4 levels were observed in type 1 diabetes (T1D). Herein, we critically examine the probable mechanisms involved in the regulation of RBP4 and TTR levels during T2D and T1D. The available evidences point to the involvement of pancreatic factors in regulating the expression of both RBP4 and TTR. It appears that during T1D, TTR levels are reduced and it exists predominantly as a monomer that may interfere its interaction with RBP4 resulting in its loss through glomerular filtration. However, plasma TTR levels remain high under T2D conditions and thus reducing glomerular filtration of RBP4. Therefore, the plasma TTR levels appear to be an important determinant of plasma RBP4 levels in these two diabetic conditions. 2012 IUBMB IUBMB Life, 64(12): 975-982, 2012

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Serum Retinol-Binding Protein Is More Highly Expressed in Visceral than in Subcutaneous Adipose Tissue and Is a Marker of Intra-abdominal Fat Mass

Cited by 365 publications

References 44 publications

Retinol-binding protein 4 in neonates born small for gestational age

Retinol-binding protein 4 in neonates born small for gestational age

Effects of Genetic Variation in the Human Retinol Binding Protein-4 Gene (RBP4) on Insulin Resistance and Fat Depot–Specific mRNA Expression

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

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