Fat-storing cells

G. Ramadori, The stellate cell (Ito-cell, fat-storing cell, lipocyte, perisinusoidal cell) of the liver. New insights into pathophysiology of an inMguing cell, Virchows Arch. [B] 67 147-158 (1991). 

A. M. Gressner, S. Lotfi, G. Gressner, E. Haltner, and J. Kropf, Synergism between hepatocytes and Kupffer cells in the activation of fat storing cells (perisinusoidal lipocytes), J. Hepatol. 79 117-132 (1993). 

Excessive intake of vitamin A (hyper-vitaminosis A), like too little intake, can result in adverse health consequences. Approximately 60%-80% of vitamin A is stored in the liver in hepatic stellate cells (also called Ito cells and fat-storing cells). Retinyl esters are the main storage form of vitamin A in the liver and are found in lipid droplets present in the hepatic... 

Ito cells (T. Ito, 1951) are also known as fat-storing cells, hepatic stellate cells or lipocytes. These long-lived cells, 5-10 im in size with long thin strands, lie in Disse s space (s. figs. 2.8, 2.9) and contain numerous cytoplasmic fat droplets as well as an abundance of vitamin A (= retinol ester). The retinol esters of the chylomicrons are absorbed by the hepatocytes and hydrolyzed into retinol. The latter is either passed to the blood by means of RBP or transported to Ito cells and stored. In the fat droplets of Ito cells, about 75% of the liver retinoids are present in the form of retinol esters. These fat droplets are characteristic of Ito cells they represent vacuolized... 

Gressner, A.M., Bachem, M.G. Cellular sources of noncollagenous matrix proteins role of fat-storing cells in fibrogenesis. Semin. Liver Dis. 1990 10 30-46... 

Vitamin A Both vitamin A (= retinol) and A2 (= 3-dehydroreti-nol) occur in nature. Like their derivatives, they are classed under the umbrella term axerophtol. The major provitamin is p-carotin. Vitamin A is stored as a lipoglycoprotein complex in the fat-storing cells of the liver. It is released when necessary by being coupled with a retinol-binding protein (RBP) and is then transported to the cells which require vitamin A. In the case of zinc deficiency the rate of RBP synthesis is markedly increased, and as a result serum retinol concentration is reduced. Retinol deficiency can be compensated by zinc substitution. The daily requirement is approx. 1 mg. (7, 36)... 

Tht fatty liver condition can be described as follows. With alcohol consumption, the liver s main source of energy (fatly acids) is replaced by alcohol. This results in accumulation of unused fatty acids, in the form of triglycerides, with the consequent deposition of these TGs as fat. This mechanism is different from the fatty liver provoked by kwashiorkor, where a fatty liver results from the failure to synthesize the apoHpopioteins needed for exporting TGs from the liver. The fatty liver of kwashiorkor is not associated with cirrhosis, but that of alcoholism is associated with conversion of stellate cells to cells resembling those of connective tissue, i-c-, fibroblasts, Stellate cells are fat-storing cells that occur In the interstitial space between the capillaries and hcpalocytcs, called the space of Disse. 

More than 90% of the body s supply of vitamin A is stored in the liver. The hepatic parenchymal cells are involved in its uptake, storage, and metabolism. Retinyl esters are transferred to hepatic fat-storing cells (also called Ito cells or lipocytes) from the parenchymal cells. The capacity of these fat-storing cells may determine when vitamin A toxicosis becomes symptomatic. During the development of hepatic fibrosis (e.g., in alcoholic liver disease), vitamin A stores in Ito cells disappear and the cells differentiate to myofibroblasts. These cells appear to be the ones responsible for the increased collagen synthesis seen in fibrotic and cirrhotic livers. 

Fatty acids are stored as triacylglycerols, primarily as droplets in adipose (fat-storing) cells. In response to hormones such as adrenaline, triacylglycerols are hydrolyzed in the cytosol to free fatty acids and glycerol ... 

The hepatic stellate (or Ito) cells are fat-storing cells found in the perisinusoidal spaces between the hepatocytes and sinusoids these cells can later become involved in hepatic fibrosis. When hepatic lipid is increased by greater than 5% by weight, the histological changes are described as steatosis, or fatty changes. 

Parola, M., M. Pinzani, A. Casini, E. Albano, G. Poli, A. Gentilini, P Gentilini, and M.U. Dianzani. 1993. Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen alpha 1 (I) gene expression in human liver fat-storing cells. Biochem. Biophys. Res. Commun. 194 1044—1050. 

Where the fat goes. The yellow cells are adipocytes, the fat-storing cells of our bodies. Each adipocyte is almost entirely composed of a single droplet of triglycerides. 

Perisinusoidal Ito cells (fat-storing cells, hepatic h-pocytes, vitamin A-storing cells) are the primary matrix-producing cells in liver fibrosis. They are difficult to visualize in standard histological preparations but can be identified in sections of rat liver by immunohistochemical detection of the intermediate filament protein desmin this protein is not expressed by other sinusoidal cells (Yokoi etal. 1984, Burt etal. 1986). 

During culture on uncoated plastic surfaces, fat storing cells loose their normal phenotype and within 1-2 weeks transform into highly productive myofibroblasts, which have the capacity to produce soluble, most profibrogenic mediators stimulating proliferation, transformation and enhanced proteoglycan synthesis of quiescent fat storing cells in a paracrine mode (Bachem etal. 1992). 

In human fiver, fat-storing cells were increased after anabolic steroid and corticosteroid therapies. 

The liver comprises several different types of cells, including the hepatic parenchymal cells, the sinusoidal cells, and cells that line the bile ductules and ducts. The sinusoidal (and perisinusoidal) cells include the Kupfier cells, the endothelial cells, and the fat-storing cells. Most of the liver, both in terms of total cell number, cell volume, and mass (total protein) is composed of parenchymal... 

Much more information is needed about the metabolic characteristics of the fat-storing cells and about the metabolic interrelationships between these cells and parenchymal cells. The mechanism whereby retinol is transferred between these two types of cells requires exploration. This mechanism may involve one of the known retinoid-binding proteins or a different protein present in the intercellular space. Studies in the authors laboratory (M. Kato and D. S. Goodman, unpublished observations) using immunohistochemical methods and antibodies specific for CRBP have shown that CRBP is concentrated in the fatstoring cells. Information is needed about the potential enzymatic capability of... 

Other factors that may affect the availability of retinol for complex formation with apo-RBP are (1) the manner in which retinol is transported within the cell from the site(s) of retinyl ester hydrolysis to a molecule of apo-RBP and (2) the manner in which the retinol molecule is presented to the membrane-bound molecule of apo-RBP. In this regard, the possible roles of cellular retinol-binding protein (CRBP) and of the so-called cytosol retinyl ester lipoprotein complex in delivering retinol to apo-RBP need exploration (Chen et al., 1981 Sklan et al., 1982). More information is also needed about the movement of retinol between hepatocytes and fat-storing cells (lipocytes) under normal and abnormal conditions. These various topics are also reviewed in Chapter 7. 

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