Dietary Vitamin A and Visceral Adiposity: A Modulating Role of the Retinol-Binding Protein 4 Gene

2015 ◽  
Vol 8 (4-6) ◽  
pp. 164-173 ◽  
Author(s):  
Katie Goodwin ◽  
Michal Abrahamowicz ◽  
Gabriel Leonard ◽  
Michel Perron ◽  
Louis Richer ◽  
...  
Keyword(s):  
Vitamin A ◽  
Binding Protein ◽  
Visceral Adiposity ◽  
Retinol Binding Protein ◽  
Dietary Vitamin ◽  
Retinol Binding Protein 4

scholarly journals Vitamin A Transporters in Visual Function: A Mini Review on Membrane Receptors for Dietary Vitamin A Uptake, Storage, and Transport to the Eye

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3987
Author(s):  
Nicasio Martin Ask ◽  
Matthias Leung ◽  
Rakesh Radhakrishnan ◽  
Glenn P. Lobo
Keyword(s):  
Cell Growth ◽  
Vitamin A ◽  
Visual Function ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Dietary Vitamin ◽  
Peripheral Tissues ◽  
Retinol Binding Protein 4 ◽  
Retinyl Esters ◽  
And Function

Vitamins are essential compounds obtained through diet that are necessary for normal development and function in an organism. One of the most important vitamins for human physiology is vitamin A, a group of retinoid compounds and carotenoids, which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in the vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids such as β-carotene from plants or preformed vitamin A such as retinyl esters from animal sources are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carotenoid cleavage oxygenases (CCOs), such as Beta-carotene 15,15’-monooxygenase (BCO1), to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein 4 receptor 2 (RBPR2) in systemic tissues (e.g., in the retina and the liver, respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to review literature regarding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.

Visceral Adiposity Is Associated with Serum Retinol Binding Protein-4 Levels in Healthy Women*

Obesity ◽  
2007 ◽  
Vol 15 (9) ◽  
pp. 2225-2232 ◽  
Author(s):  
Ji-Won Lee ◽  
Jee-Aee Im ◽  
Hye-Ree Lee ◽  
Jae-Yong Shim ◽  
Byung-S. Youn ◽  
...  
Keyword(s):  
Binding Protein ◽  
Visceral Adiposity ◽  
Retinol Binding Protein ◽  
Serum Retinol ◽  
Retinol Binding Protein 4 ◽  
Healthy Women

Retinol binding protein 4 and its membrane receptors: a metabolic perspective

2015 ◽  
Vol 22 (1) ◽  
Author(s):  
Ronja Fedders ◽  
Matthias Muenzner ◽  
Michael Schupp
Keyword(s):  
Metabolic Diseases ◽  
Binding Protein ◽  
Current Data ◽  
Membrane Receptors ◽  
Retinol Binding Protein ◽  
Metabolic Effects ◽  
Retinol Binding Protein 4 ◽  
Underlying Mechanisms

AbstractNearly a decade of intense research has passed since the first report linking circulating retinol binding protein 4 (RBP4) to the development of insulin resistance. By now, a variety of underlying mechanisms have been identified; some of them are adherent to the canonical role of this circulating protein, which is to transport and deliver retinol to target tissues, and others that seem rather independent of retinol transport. Despite all these efforts, a consensus in the basic principles of RBP4’s metabolic effects has not been reached and some controversy remains. Using this as an opportunity, we here review and discuss current data on RBP4’s action on insulin sensitivity and its dependency on retinol homeostasis. We pay special attention to the involvement of RBP4 membrane receptors that were identified during these years, such as ‘stimulated by retinoic acid 6’ (STRA6), and whose identification added another layer of complexity to RBP4’s diverse actions. A better understanding of RBP4’s functions might allow its therapeutic exploitations, urgently needed in our period that is defined by an epidemic increase in metabolic diseases such as obesity and type 2 diabetes.

Decreased levels of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension

Cephalalgia ◽  
2016 ◽  
Vol 36 (14) ◽  
pp. 1379-1384 ◽  
Author(s):  
Kathrin Doppler ◽  
Morten Schütt ◽  
Claudia Sommer
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Binding Protein ◽  
Aquaporin 4 ◽  
Retinol Binding Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Increased Intracranial Pressure ◽  
Retinol Binding Protein 4

Background Idiopathic intracranial hypertension is characterized by increased intracranial pressure. Its pathogenesis is largely unknown. Aquaporins may play a role in the homeostasis of cerebrospinal fluid. Methods We aimed to elucidate the role of aquaporins in idiopathic intracranial hypertension by measuring the level of aquaporin-1 and aquaporin-4 in the cerebrospinal fluid and plasma of 28 patients and 29 controls by enzyme-linked immunosorbent assay. The adipokines leptin and retinol-binding protein 4 were also measured. Results We found a reduction in aquaporin-4 in the cerebrospinal fluid of patients. Leptin levels were increased in the cerebrospinal fluid and plasma of patients and were correlated with weight, body mass index and body fat. There was no difference between patients and controls in the levels of aquaporin-4 and retinol-binding protein 4. Conclusion Our data suggest that an imbalance of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension may contribute to the pathogenesis of this disorder.

scholarly journals A Functional Binding Domain in the Rbpr2 Receptor is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish

2020 ◽  
Author(s):  
Ashish K. Solanki ◽  
Altaf A Kondkar ◽  
Joseph Fogerty ◽  
Yanhui Su ◽  
Seok-hyung Kim ◽  
...  
Keyword(s):  
Vitamin A ◽  
Cell Survival ◽  
Photoreceptor Cell ◽  
Binding Protein ◽  
Binding Domain ◽  
Human Vision ◽  
Retinol Binding Protein ◽  
Dietary Vitamin ◽  
Binding Residues ◽  
Vitamin A Transport

Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is however not expressed in systemic tissues, where there is high-affinity RBP4 binding and ROL uptake. We tested the hypothesis, that the second retinol-binding protein 4 receptor 2 (Rbpr2) which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, that were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatments rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival.

scholarly journals Retinol Binding Protein 4 Levels relate to the presence and severity of coronary artery disease

2021 ◽  
Author(s):  
Gokay Nar ◽  
Sara Cetin Sanlialp ◽  
Rukiye Nar
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Serum Retinol ◽  
Retinol Binding Protein 4 ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
The Relationship

Background: The prevous studies has showed that serum retinol binding protein 4 (RBP4) levels increased in metobolic disorders which are closely associated with cardiovascular dieases (CVD).  However the human studies investigating the role of RBP4 in CVD are conflicted. Therefore, we aimed to evaluate the relationship between RBP4 and the presence and the severity of coronary artery disease (CAD) in this study. Methods: 55 patients with presenting acute coronary syndrome (ACS) and 43 control subjects who had various cardiovascular risk factors with normal coronary artery on coronary angiography were included in this study.The serum RBP4 concentrations were measured using ELISA method and clinically and anatomically score models were used to asses the severity of coronary lesion. Results: Serum RBP4 level was significantly higher in patients with ACS compared to the controls (68.40 ± 47.94 mg/L vs. 49.46 ± 13.64 mg/L; p = 0.014).  RBP4 was correlated with GENSINI and SYNTAX I score (r = 0,286 p=0,034; r = 0.403 p = 0.002 respectively). However, there was no relationship between RBP4 and GRACE score. Conclusion: Patients with ACS had increased serum RBP4 levels and its high levels were correlated with CAD severity.

scholarly journals A Functional Binding Domain in the Rbpr2 Receptor Is Required for Vitamin A Transport, Ocular Retinoid Homeostasis, and Photoreceptor Cell Survival in Zebrafish

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1099
Author(s):  
Ashish K. Solanki ◽  
Altaf A. Kondkar ◽  
Joseph Fogerty ◽  
Yanhui Su ◽  
Seok-Hyung Kim ◽  
...  
Keyword(s):  
Vitamin A ◽  
Cell Survival ◽  
Photoreceptor Cell ◽  
Binding Protein ◽  
Binding Domain ◽  
Human Vision ◽  
Retinol Binding Protein ◽  
Dietary Vitamin ◽  
Binding Residues ◽  
Vitamin A Transport

Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is, however, not expressed in systemic tissues, where there is high affinity RBP4 binding and ROL uptake. We tested the hypothesis that the second retinol binding protein 4 receptor 2 (Rbpr2), which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR-generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, which were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatment rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival.

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