scholarly journals Transplacental delivery of retinoid: the role of retinol-binding protein and lipoprotein retinyl ester

2004 ◽  
Vol 286 (5) ◽  
pp. E844-E851 ◽  
Author(s):  
Loredana Quadro ◽  
Leora Hamberger ◽  
Max E. Gottesman ◽  
Vittorio Colantuoni ◽  
Rajasekhar Ramakrishnan ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Congenital Malformations ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Wild Type ◽  
Maternal Circulation ◽  
Retinyl Ester ◽  
Retinyl Esters ◽  
Normal Embryonic Development

Retinoids are required for normal embryonic development. Both embryonic retinoid deficiency and excess result in congenital malformations. There is little understanding of the physiology underlying retinoid transfer from the maternal circulation to the embryo. We now report studies that explore this process using retinol-binding protein-deficient (RBP−/−) mice and mice that express human RBP on the RBP−/−background. Our studies establish that dietary retinoid, bound to lipoproteins, can serve as an important source for meeting tissue retinoid requirements during embryogenesis. Indeed, retinyl ester concentrations in the circulations of pregnant RBP−/−mice are significantly elevated over those observed in wild-type mice, suggesting that lipoprotein retinyl esters may compensate for the absence of retinol-RBP during pregnancy. We also demonstrate, contrary to earlier proposals, that maternal RBP does not cross the placenta and cannot enter the fetal circulation. Overall, our data indicate that both retinol-RBP and retinyl esters bound to lipoproteins are able to provide sufficient retinoid to the embryo to allow for normal embryonic development.

scholarly journals Characterization of liver stellate cell retinyl ester storage

1994 ◽  
Vol 300 (3) ◽  
pp. 793-798 ◽  
Author(s):  
G Trøen ◽  
A Nilsson ◽  
K R Norum ◽  
R Blomhoff
Keyword(s):  
Fatty Acid ◽  
Binding Protein ◽  
Stellate Cells ◽  
The Body ◽  
Retinol Binding Protein ◽  
Storage Site ◽  
Retinyl Ester ◽  
Cellular Content ◽  
Retinyl Esters ◽  
Cultivation In Vitro

The stellate cells of the liver are the main storage site of retinyl esters in the body. During cultivation in vitro of stellate cells isolated from rat and rabbit livers were observed that the cells rapidly loose their retinyl ester content. Freshly isolated stellate cells contain about 144 nmol of total retinol/mg of protein, while cells cultivated for 14 days contained below 0.1 nmol/mg of protein. When 3-day-old cultures were incubated for 6 h with 2 microM retinol, the cellular content increased from 5.6 to approx. 9.4 nmol of total retinyl esters/mg of protein. In contrast, little retinyl ester accumulated in 10-20-day-old cultures incubated with 2 microM retinol. At 50 microM retinol, however, the retinyl ester level did increase both with 3-day-old cultures and 10-20-day-old cultures. In parallel experiments with cultured fibroblasts esterification characteristics similar to those seen in older cultures of stellate cells were observed. When 10-day-old cultures of stellate cells were incubated with retinol alone, or in combination with palmitic acid, linoleic acid or oleic acid, the total storage of retinyl esters increased by 20-150%. In most cases, the fatty acid supplemented in the medium was found to be the dominant fatty acid esterified with retinol. Cultures of stellate cells were then exposed to a physiological concentration (1.3 microM) of radioactive retinol free in solution or bound to retinol-binding protein. With 3-day-old cultures, as well as older cultures, the cellular content of unesterified retinol was 10-20 times higher when free retinol was added compared with addition of retinol bound to retinol-binding protein. However, 2-3-fold as much radioactive retinyl esters were recovered in cells incubated with retinol-retinol-binding protein compared with retinol free in solution. These results show that retinol delivered to stellate cells from retinol-binding protein is preferentially esterified, and that the complex is handled differently to free retinol by the stellate cells.

scholarly journals Multiple pathways ensure retinoid delivery to milk: studies in genetically modified mice

2010 ◽  
Vol 298 (4) ◽  
pp. E862-E870 ◽  
Author(s):  
Sheila M. O'Byrne ◽  
Yuko Kako ◽  
Richard J. Deckelbaum ◽  
Inge H. Hansen ◽  
Krzysztof Palczewski ◽  
...  
Keyword(s):  
Normal Growth ◽  
Retinyl Palmitate ◽  
Postnatal Period ◽  
Retinol Binding Protein ◽  
Wild Type ◽  
Retinyl Ester ◽  
Ester Formation ◽  
Fatty Acid Transporter ◽  
Retinyl Esters ◽  
Lecithin:Retinol Acyltransferase

Retinoids are absolutely required for normal growth and development during the postnatal period. We studied the delivery of retinoids to milk, availing of mouse models modified for proteins thought to be essential for this process. Milk retinyl esters were markedly altered in mice lacking the enzyme lecithin:retinol acyltransferase ( Lrat−/−), indicating that this enzyme is normally responsible for the majority of retinyl esters incorporated into milk and not an acyl-CoA dependent enzyme, as proposed in the literature. Unlike wild-type milk, much of the retinoid in Lrat−/− milk is unesterified retinol, not retinyl ester. The composition of the residual retinyl ester present in Lrat−/− milk was altered from predominantly retinyl palmitate and stearate to retinyl oleate and medium chain retinyl esters. This was accompanied by increased palmitate and decreased oleate in Lrat−/− milk triglycerides. In other studies, we investigated the role of retinol-binding protein in retinoid delivery for milk formation. We found that Rbp−/− mice maintain milk retinoid concentrations similar to those in matched wild-type mice. This appears to arise due to greater postprandial delivery of retinoid, a lipoprotein lipase (LPL)-dependent pathway. Importantly, LPL also acts to assure delivery of long-chain fatty acids (LCFA) to milk. The fatty acid transporter CD36 also facilitated LCFA but not retinoid incorporation into milk. Our data show that compensatory pathways for the delivery of retinoids ensure their optimal delivery and that LRAT is the most important enzyme for milk retinyl ester formation.

scholarly journals Cellular retinol-binding protein type III is a PPARγ target gene and plays a role in lipid metabolism

2008 ◽  
Vol 295 (6) ◽  
pp. E1358-E1368 ◽  
Author(s):  
Cynthia F. Zizola ◽  
Gary J. Schwartz ◽  
Silke Vogel
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Free Fatty Acid ◽  
Target Gene ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Wild Type ◽  
Type Iii ◽  
Cellular Retinol Binding Protein

Cellular retinol-binding protein (CRBP) type III (CRBP-III) belongs to the family of intracellular lipid-binding proteins, which includes the adipocyte-binding protein aP2. In the cytosol, CRBP-III binds retinol, the precursor of retinyl ester and the active metabolite retinoic acid. The goal of the present work is to understand the regulation of CRBP-III expression and its role in lipid metabolism. Using EMSAs, luciferase reporter assays, and chromatin immunoprecipitation assays, we found that CRBP-III is a direct target of peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, CRBP-III expression was induced in adipose tissue of mice after treatment with the PPARγ agonist rosiglitazone. To examine a potential role of CRBP-III in regulating lipid metabolism in vivo, CRBP-III-deficient (C-III-KO) mice were maintained on a high-fat diet (HFD). Hepatic steatosis was decreased in HFD-fed C-III-KO compared with HFD-fed wild-type mice. These differences were partly explained by decreased serum free fatty acid levels and decreased free fatty acid efflux from adipose tissue of C-III-KO mice. In addition, the lack of CRBP-III was associated with reduced food intake, increased respiratory energy ratio, and altered body composition, with decreased adiposity and increased lean body mass. Furthermore, expression of genes involved in mitochondrial fatty acid oxidation in brown adipose tissue was increased in C-III-KO mice, and C-III-KO mice were more cold tolerant than wild-type mice fed an HFD. In summary, we demonstrate that CRBP-III is a PPARγ target gene and plays a role in lipid and whole body energy metabolism.

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.

Role of the HOXA cluster in HSC emergence and blood cancer

2021 ◽  
Author(s):  
Mays Abuhantash ◽  
Emma M. Collins ◽  
Alexander Thompson
Keyword(s):  
Embryonic Development ◽  
Hox Genes ◽  
Hoxa Cluster ◽  
Hematopoietic Stem ◽  
Blood Cancer ◽  
Non Coding Rna ◽  
Blood Formation ◽  
Peripheral Cells ◽  
Normal Embryonic Development

Hematopoiesis, the process of blood formation, is controlled by a complex developmental program that involves intrinsic and extrinsic regulators. Blood formation is critical to normal embryonic development and during embryogenesis distinct waves of hematopoiesis have been defined that represent the emergence of hematopoietic stem or progenitor cells. The Class I family of homeobox (HOX) genes are also critical for normal embryonic development, whereby mutations are associated with malformations and deformity. Recently, members of the HOXA cluster (comprising 11 genes and non-coding RNA elements) have been associated with the emergence and maintenance of long-term repopulating HSCs. Previous studies identified a gradient of HOXA expression from high in HSCs to low in circulating peripheral cells, indicating their importance in maintaining blood cell numbers and differentiation state. Indeed, dysregulation of HOXA genes either directly or by genetic lesions of upstream regulators correlates with a malignant phenotype. This review discusses the role of the HOXA cluster in both HSC emergence and blood cancer formation highlighting the need for further research to identify specific roles of these master regulators in normal and malignant hematopoiesis.

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