Vitamin A metabolism in rat liver: a kinetic model

1993 ◽  
Vol 264 (3) ◽  
pp. G509-G521
Author(s):  
M. H. Green ◽  
J. B. Green ◽  
T. Berg ◽  
K. R. Norum ◽  
R. Blomhoff
Keyword(s):  
Vitamin A ◽  
Binding Protein ◽  
Compartmental Analysis ◽  
Stellate Cells ◽  
Cell Types ◽  
Isolated Hepatocytes ◽  
Retinol Binding Protein ◽  
Nonparenchymal Cells ◽  
Vitamin A Metabolism ◽  
Retinyl Esters

Vitamin A metabolism in the liver involves both hepatocytes and the nonparenchymal perisinusoidal stellate cells. To describe and quantitate the dynamic relationships between retinol in these cells and in plasma, we administered either chylomicrons labeled with [3H]retinyl esters or plasma containing [3H]retinol-retinol-binding protein-transthyretin to rats. Radioactivity and retinol masses were measured in plasma, liver, and isolated hepatocytes for 15 days; data were analyzed by model-based compartmental analysis. The resulting model predicts that: 1) approximately 20% of the total plasma turnover of retinol goes to the liver (vs. nonhepatic tissues) and approximately 20% of plasma retinol input is from liver (vs. nonhepatic tissues), 2) about one-half of the retinol recycling from plasma to liver is taken up by hepatocytes and about one-half by nonparenchymal cells, 3) retinyl esters in both cell types are derived preferentially from newly taken up retinol rather than from the main intracellular retinol pools, and 4) at least one-half of the retinol secreted by hepatocytes of rats consuming low levels of vitamin A is directly transferred to nonparenchymal cells. In addition, the data are compatible with the hypothesis that retinol-binding protein is the vehicle for transfer of retinol from hepatocytes to nonparenchymal stellate cells and between plasma and liver cells.

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.

scholarly journals Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies

2019 ◽  
Vol 11 (3) ◽  
pp. 644-666 ◽  
Author(s):  
Thomas Olsen ◽  
Rune Blomhoff
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Binding Protein ◽  
Human Studies ◽  
Retinol Binding Protein ◽  
Retinol Binding Protein 4 ◽  
Vitamin A Metabolism

ABSTRACT Vitamin A is a fat-soluble essential nutrient obtained from plant- and animal-based sources that has roles in growth, vision, and metabolism. Vitamin A circulates mainly as retinol bound to retinol-binding protein 4 (RBP4), and is delivered to tissues and converted to retinoic acid, which is a ligand for several nuclear receptors. In recent years, aspects of vitamin A metabolism have been under scrutiny with regards to the development of metabolic and lifestyle diseases including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and overweight and obesity in humans. Studies have mainly focused on RBP4 in this context, whereas the major circulating form, retinol, and the major bioactive form, retinoic acid, have been overlooked in this regard until recently. As one of the main roles of RBP4 is to deliver retinol to tissues for biological action, the associations of retinol and retinoic acid with these diseases must also be considered. In this review, we summarize and discuss recent and available evidence from human studies with focus on retinol, retinoic acid, and RBP4 and provide an overview of these crucial components of vitamin A metabolism in CVD, T2DM, and obesity. In summary, retinol was found to be both inversely and positively associated with CVD whereas the associations with T2DM and obesity were less clear. Although only a few studies have been published on retinoic acid, it was inversely associated with CVD. In contrast, serum RBP4 was mostly found to be positively associated with CVD, T2DM, and obesity. At present, it is difficult to ascertain why the reported associations differ depending on the compound under study, but there is a clear imbalance in the literature in disfavor of retinol and retinoic acid, which needs to be considered in future human studies.

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 Retinol esterification in cultured rat liver cells

1985 ◽  
Vol 230 (3) ◽  
pp. 617-623 ◽  
Author(s):  
C A Drevon ◽  
R Blomhoff ◽  
M Rasmussen ◽  
G M Kindberg ◽  
T Berg ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Vitamin A ◽  
Marked Decrease ◽  
Stellate Cells ◽  
Cell Types ◽  
Retinyl Palmitate ◽  
Cultured Hepatocytes ◽  
Rat Liver Cells ◽  
Order Of Magnitude ◽  
Retinyl Esters

Retinol esterification was examined in cultured hepatocytes and stellate cells from the rat. Esterification of [3H]retinol was linear for 2 h in both cell types. By increasing the concentration of retinol in the medium, there was a marked increase in retinol esterification in both cell types. The capacity for esterification of retinol was in the same order of magnitude in the two cell types at 3.5 microM-retinol in the medium. This represents a rate of retinol esterification which far exceeds that required to esterify the amount of retinol absorbed in the intestine. It was demonstrated in particulate homogenates from cultured hepatocytes that the esterification of retinol was dependent on acyl-CoA. Addition of 25-hydroxycholesterol or mevalonolactone promoted an increase in cholesterol esterification, whereas retinol esterification was unaffected, suggesting that cholesterol and retinol are esterified by two different enzymes. Some 80% of vitamin A in cultured hepatocytes is retinyl esters, mostly retinyl palmitate. By adding 87 microM-retinol in the medium the cells accumulated 100-fold free retinol and 2.5-3.0-fold retinyl esters within 1 h. When retinol-loaded cells were incubated without retinol, there was a marked decrease especially in free but also in esterified retinol. In the presence of 1 mM-oleic acid in the medium the amount of retinyl oleate was twice that in control cells.

Understanding the physiological role of retinol-binding protein in vitamin A metabolism using transgenic and knockout mouse models

2003 ◽  
Vol 24 (6) ◽  
pp. 421-430 ◽  
Author(s):  
Loredana Quadro ◽  
Leora Hamberger ◽  
Vittorio Colantuoni ◽  
Max E. Gottesman ◽  
William S. Blaner
Keyword(s):  
Vitamin A ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Binding Protein ◽  
Physiological Role ◽  
Retinol Binding Protein ◽  
Vitamin A Metabolism
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