scholarly journals Minireview: Obesity and LipOdystrophy—Where Do the Circles Intersect?

Endocrinology ◽  
2008 ◽  
Vol 149 (3) ◽  
pp. 925-934 ◽  
Author(s):  
Farid F. Chehab
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Retinol Binding Protein 4 ◽  
Secreted Factors ◽  
Survival And Reproduction

Adipose tissue is unique in that it can undergo significant hypertrophy and atrophy, resulting in wide ranges of obesities and lipodystrophies. At the base of this elasticity is the lipid-filled adipocyte, which can either overfill by storing large amounts of triglycerides or shrink to a tiny cell by depleting its lipids and as such is remarkable in sustaining insults. As a major energy reservoir, the adipocyte may hold considerable calories necessary for survival and reproduction, two functions that are essential for the survival of the species. This review will summarize some of the recent studies that have advanced our understanding of the central and peripheral mechanisms that are initiated by adipocyte-secreted factors such as leptin, adiponectin, resistin, and retinol-binding protein 4. The intersection of obesity and lipodystrophy results in insulin resistance, which may be unlocked by elucidating the roles of these factors in pathways that control insulin sensitivity and glucose uptake.

Fenofibrate reduces serum retinol-binding protein-4 by suppressing its expression in adipose tissue

2009 ◽  
Vol 296 (4) ◽  
pp. E628-E634 ◽  
Author(s):  
Haiya Wu ◽  
Li Wei ◽  
Yuqian Bao ◽  
Junxi Lu ◽  
Ping Huang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Mrna Levels ◽  
Retinol Binding Protein 4 ◽  
Fenofibrate Treatment ◽  
Obese Rats

Fenofibrate is a peroxisome proliferator-activated receptor-α (PPARα) activator that has been clinically used to treat dyslipidemia and insulin resistance. To better understand the molecular mechanisms underlying fenofibrate action, we investigated whether fenofibrate affects serum levels of retinol-binding protein-4 (RBP4), an adipocytokine that has recently been shown to link obesity and insulin resistance. Fenofibrate treatment significantly decreased serum RBP4 levels of dyslipidemic patients, which correlated with reduced body weight and increased insulin sensitivity. To elucidate the biochemical mechanisms of fenofibrate action, we investigated the effect of fenofibrate on RBP4 expression in obese rats. Fenofibrate greatly decreased RBP4 mRNA levels in adipose tissue but not in the liver, which correlated with decreased serum RBP4 levels and increased insulin sensitivity in obese rats. Consistent with a direct effect on RBP4 expression, fenofibrate treatment significantly reduced the mRNA expression levels of RPB4 in 3T3-L1 adipocytes. Together, our results demonstrate for the first time that fenofibrate inhibits RPB4 expression in dyslipidemic human subjects and suggest that inhibition of RBP4 expression in adipocytes may provide a mechanism by which fenofibrate improves insulin sensitivity in dyslipidemic patients.

scholarly journals Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

2015 ◽  
Vol 35 (2) ◽  
pp. 778-788 ◽  
Author(s):  
Chaoyu Zhu ◽  
Yuanyuan Xiao ◽  
Xiaohua Liu ◽  
Junfeng Han ◽  
Jianmei Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Oral Glucose ◽  
Serum Retinol ◽  
Retinol Binding Protein 4 ◽  
Obese Rats ◽  
Pioglitazone Treatment

Background/Aims: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance. Methods: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. Results: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. Conclusion: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.

scholarly journals Ghrelin- and GH-induced insulin resistance: no association with retinol-binding protein-4

2013 ◽  
Vol 2 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Esben Thyssen Vestergaard ◽  
Morten B Krag ◽  
Morten M Poulsen ◽  
Steen B Pedersen ◽  
Niels Moller ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Binding Protein ◽  
Human Subjects ◽  
Retinol Binding Protein ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Retinol Binding Protein 4 ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

ObjectiveSupraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.Materials and methodsTo study GH-independent effects of ghrelin, seven hypopituitary men undergoing replacement therapy with GH and hydrocortisone were given ghrelin (5 pmol/kg per min) and saline infusions for 300 min in a randomized, double-blind, placebo-controlled, crossover design. Circulating RBP4 levels were measured at baseline and during a hyperinsulinemic–euglycemic clamp on both study days. To study the direct effects of GH, nine healthy men were treated with GH (2 mg at 2200 h) and placebo for 8 days in a randomized, double-blind, placebo-controlled, crossover study. Serum RBP4 levels were measured before and after treatment, and insulin sensitivity was measured by the hyperinsulinemic–euglycemic clamp technique.ResultsGhrelin acutely decreased peripheral insulin sensitivity. Serum RBP4 concentrations decreased in response to insulin infusion during the saline experiment (mg/l): 43.2±4.3 (baseline) vs 40.4±4.2 (clamp), P<0.001, but this effect was abrogated during ghrelin infusion (mg/l): 42.4±4.5 (baseline) vs 42.9±4.7 (clamp), P=0.73. In healthy subjects, serum RBP4 levels were not affected by GH administration (mg/l): 41.7±4.1 (GH) vs 43.8±4.6 (saline), P=0.09, although GH induced insulin resistance.Conclusionsi) Serum RBP4 concentrations decrease in response to hyperinsulinemia, ii) ghrelin abrogates the inhibitory effect of insulin on circulating RBP4 concentrations, and iii) ghrelin as well as GH acutely induces insulin resistance in skeletal muscle without significant changes in circulating RBP4 levels.

Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases

2008 ◽  
Vol 114 (4) ◽  
pp. 275-288 ◽  
Author(s):  
Herbert Tilg ◽  
Alexander R. Moschen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Clinical Medicine ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Acid Oxidation ◽  
Endothelial Cell Function ◽  
Retinol Binding Protein 4 ◽  
Associated Diseases ◽  
Anti Inflammatory

Obesity and obesity-related disorders play an important role in clinical medicine. Adipose tissue, with its soluble mediators called adipocytokines, has emerged as a major endocrine organ. These adipocytokines comprise many mediators such as adiponectin, PBEF (pre-B-cell-enhancing factor)/visfatin, leptin, resistin, retinol-binding protein-4 and others. They play major roles in key aspects of metabolism, such as insulin resistance, fatty acid oxidation, inflammation and immunity. Adiponectin, a prototypic adipocytokine, is of importance in the regulation of insulin resistance, as circulating levels are decreased in obesity and diseases associated with insulin resistance. Besides its major role in regulation of insulin sensitivity, recent evidence suggests potent anti-inflammatory functions for adiponectin. These effects are paralleled by other immune-regulatory properties, such as regulation of endothelial cell function. The in vitro effects of adiponectin have been corroborated by several studies demonstrating potent in vivo anti-inflammatory effects. Many other adipocytokines, such as PBEF/visfatin, leptin, resistin or retinol binding protein-4, are involved in the physiology and pathophysiology of adipocytes, adipose tissue and related diseases. PBEF/visfatin, another recently characterized adipocytokine, has been linked to several inflammatory disease states beyond insulin resistance, such as acute lung injury or inflammatory bowel diseases. It has been recognized for many decades that obesity is accompanied by an increase in cancer and potentially some immune-mediated diseases. Understanding this new exciting world of adipocytokines will be of importance in the development of novel therapies for obesity-associated diseases.

scholarly journals Associations between Tissue Visfatin/Nicotinamide, Phosphoribosyltransferase (Nampt), Retinol Binding Protein-4, and Vaspin Concentrations and Insulin Resistance in Morbidly Obese Subjects

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Zeynep Goktas ◽  
Shannon Owens ◽  
Mallory Boylan ◽  
David Syn ◽  
Chwan-Li Shen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Morbidly Obese ◽  
Tissue Samples ◽  
Blood Concentrations ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Retinol Binding Protein 4 ◽  
Obese Subjects

Visfatin/Nampt, vaspin, and retinol binding protein-4 (RBP-4) play an important role in insulin resistance. The objectives of this study were to measure visfatin/Nampt, vaspin, and RBP-4 concentrations in blood, liver, muscle, subcutaneous, omental, and mesenteric adipose tissues in morbidly obese subjects and investigate their relationship to insulin resistance. Blood and tissue samples were collected from 38 morbidly obese subjects during Roux-en-Y surgery. Insulin resistance biomarkers were measured using standard kits. Visfatin/Nampt, vaspin, and RBP-4 gene expression levels in tissues were measured using real-time PCR. Their protein concentrations in blood and tissues were measured using ELISA kits. Diabetic subjects had significantly higher homeostasis model of assessment-insulin resistance and age and lower blood HDL-cholesterol concentrations than nondiabetic and prediabetic subjects. Diabetic and prediabetic subjects had significantly higher blood concentrations of visfatin/Nampt and vaspin than nondiabetic subjects. Liver RBP-4 concentrations were positively associated with blood glucose concentrations. Blood insulin resistance biomarker levels were positively associated with visfatin/Nampt concentrations in omental adipose tissue and liver, and vaspin concentrations in mesenteric adipose tissue. In conclusion, the correlations of visfatin/Nampt, vaspin, and RBP-4 with insulin resistance are tissue dependent.

scholarly journals Visceral Adipose Tissue was Associated with Increased Risk of Insulin Resistance in Lean Polycystic Ovarian Syndrome, Independent with Retinol Binding Protein-4

2020 ◽  
pp. 168-173
Author(s):  
Vita Silvana ◽  
Andon Hestiantoro ◽  
Muharam Natadisastra ◽  
Kanadi Sumapraja ◽  
Budi Wiweko
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Visceral Adipose Tissue ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Receiver Operating Curve ◽  
Retinol Binding Protein 4 ◽  
Visceral Adipose

Objective: To determine whether visceral adipose tissue or serum RBP-4 were related with the risk increment of insulin resistance in normal BMI PCOS patients. Methods: This was a cross-sectional study conducted in normal body mass index PCOS patients at Yasmin Clinic, RSCM, Jakarta from July 2014 until March 2015. Diagnosis of PCOS was established using Rotterrdam (2003) criteria. Insulin resistance was confirmed by using ratio of HOMA-IR >1.4. Results: Among 40 subjects, 20 subjects (50%) belong insulin resistance group. Serum RBP-4 level was higher in insulin resistance group (p=0.06). After ROC analysis was conducted, area under curve for of serum RBP-4 was 69.9% (CI 95% -3754.77 - (186.60-7696.14, p=0.061)). Cut-off level of serum RBP-4 was 23814.5 ng/mL yielded sensitivity and specificity to a level of 60% and 60%, respectively. After logistic regression were analyzed, visceral adipose tissue demonstrated substantial association with the risk increment of insulin resistance in normal BMI PCOS patients. Conclusions: Visceral adipose tissue demonstrated substantial association with the risk increment of insulin resistance in normal BMI PCOS patients, independent with serum RBP-4 levels. Key words: body mass index, diagnosis, insulin resistance, PCOS, retinol binding protein-4   Abstrak Tujuan: Untuk menentukan apakah jaringan adiposa viseral atau serum RBP-4 berhubungan dengan peningkatan risiko resistensi insulin pada Sindrom Ovarium Polikistik dengan indeks masa tubuh normal. Metode: Studi potong lintang dilakukan pada subjek SOPK dengan IMT normal di Klinik Yasmin, RSCM, Jakarta sejak Juli 2014 sampai dengan Maret 2015. Penegakan diagnosis SOPK dilakukan dengan kriteria Rotterdam (2003). Resistensi insulin dikonfirmasi dengan pemeriksaan rasio HOMA-IR > 1.4 Hasil: Diantara 40 subjek, sebanyak 20 subjek (50%) mengalami resistensi insulin. Kadar serum RBP-4 lebih tinggi pada kelompok resistensi insulin (p=0.06). Setelah dilakukan analisis Receiver Operating Curve (ROC), serum RBP-4 memiliki Area Under the Curve  (AUC) sebesar 69.9% (IK 95% -3754.77 - (186.60-7696.14, p=0,061)). Titik potong kadar serum RBP-4 adalah 23814.5 ng/mL dengan sensitivitas dan spesifisitas masing-masing 60% dan 60%. Setelah dilakukan analisis regresi logistik, jaringan adiposa viseral menunjukan asosiasi yang kuat dengan terjadinya resistensi insulin pada pasien SOPK dengan IMT normal. Kesimpulan: Jaringan adiposa viseral menunjukan asosiasi yang kuat dengan terjadinya resistensi insulin pada SOPK dengan IMT normal, independen terhadap kadar serum RBP-4. Kata kunci: diagnosis, indeks masa tubuh, resistensi insulin, retinol binding protein-4, SOPK

scholarly journals Is retinol binding protein 4 a link between adiposity and cancer?

2015 ◽  
Vol 23 (2) ◽  
Author(s):  
Noa Noy ◽  
Li Li ◽  
Matthew V. Abola ◽  
Nathan A. Berger
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Binding Protein ◽  
The Body ◽  
Retinol Binding Protein ◽  
Retinol Binding Protein 4 ◽  
Oncogenic Pathways ◽  
Available Information ◽  
Obesity And Cancer

AbstractRetinol binding protein 4 (RBP4) is synthesized in the liver where it binds vitamin A, retinol, and transports it to tissues throughout the body. It has been shown in some studies that the level of circulating RBP4 increases with body mass, and the protein has been implicated as a mediator in the development of insulin resistance and the metabolic disease. Adipose tissue serves as another site of RBP4 synthesis, accounting for its designation as an adipokine. In addition to its function as a transport protein, RBP4 serves as a signaling molecule which, by binding to the membrane receptor STRA6, triggers downstream activation of pro-oncogenic pathways including JAK2/STAT3/5. Taken together, available information suggests the possibility that RBP4 may be a link between obesity and cancer.

scholarly journals Retinol-binding protein-4 is not strongly associated with insulin sensitivity in normal pregnancies.

2008 ◽  
Vol 159 (1) ◽  
pp. 49-54 ◽  
Author(s):  
T Ueland ◽  
T Dalsoren ◽  
N Voldner ◽  
K Godang ◽  
T Henriksen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fat Mass ◽  
Binding Protein ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
Retinol Binding Protein ◽  
Oral Glucose ◽  
Retinol Binding Protein 4 ◽  
The Impact

ObjectiveRecently, experimental and clinical studies suggest that retinol-binding protein-4 (RBP4) may provide a link between obesity and insulin resistance. However, no previous studies have investigated the impact of circulating RBP4 on measures of insulin resistance in normal pregnant women, and the objective of this study is to measure serum RBP4 in early and late pregnancy and relate these to measures of insulin resistance and secretion controlling for changes in fat mass.Design and methodsSamples were obtained during oral glucose tolerance test (OGTT) from 44 normal pregnancies at weeks 14–16 and 30–32. Measures of fat mass were body mass index (BMI) and leptin while insulin sensitivity and secretion were predicted from OGTT. Leptin and RPB4 were measured by immunoassay.ResultsInsulin sensitivity decreased during the course of pregnancy. Insulin sensitivity and secretion were best explained by BMI and circulating leptin, but not RBP4, both in early and late pregnancy. However, a marked increase in fasting RBP4 from early to late pregnancy was observed, and this change was associated with a decline in insulin sensitivity. A marked increase in RBP4 was found during OGTT at weeks 14–16 with an opposite temporal course at weeks 30–32.ConclusionThe increased fat mass and insulin resistance during normal pregnancy was best explained by measures of fat mass. However, the increase in RBP4 from early to late pregnancy, associated with a decline in insulin sensitivity, potentially indicates interactions with glucose metabolism.

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