Abstract
Hepatic stellate cells store the majority of the liver's retinoid (vitamin A) reserves as retinyl esters in stellate cell lipid droplets. A study was conducted to explore the effects of differences in dietary retinoid and triglyceride intake on the composition of the stellate cell lipid droplets. Weanling rats were placed on one of five diets that differed in retinoid or triglyceride contents. The dietary groups were: 1) control (2.4 mg retinol (as retinyl acetate)/kg diet and 20.5% of the calories supplied by triglyceride (as peanut oil]; 2) low retinol (0.6 mg retinol/kg diet and control triglyceride levels); 3) high retinol (24 mg retinol/kg diet and control triglyceride levels); 4) low triglyceride (2.4 mg retinol/kg diet and 5% of the calories supplied by triglyceride); and 5) high triglyceride (2.4 mg retinol/kg diet and 45% of the calories supplied by triglyceride). Stellate cells were isolated using the pronase-collagenase method and stellate cell lipid droplets were isolated by differential centrifugation. The levels of retinoids and other lipids were measured by high performance liquid chromatography. The stellate cells from control rats contained 113 micrograms total lipid/10(6) cells. Control stellate cell lipid droplets had the following mean percent lipid composition: 39.5% retinyl ester; 31.7% triglyceride; 15.4% cholesteryl ester; 4.7% cholesterol; 6.3% phospholipids; and 2.4% free fatty acids. Both the concentration of stellate cell lipids and the composition of stellate cell lipid droplets were markedly altered by changes in dietary retinoid. The low and high retinol groups contained, respectively, 82 and 566 micrograms total lipid/10(6) cells, with retinyl ester representing, respectively, 13.6% and 65.4% of the lipid present in the stellate cell lipid droplets. Low and high triglyceride groups were similar to controls in both stellate cell lipid content and the composition of the stellate cell lipid droplets. These findings indicate that the composition of stellate cell lipid droplets is strongly regulated by dietary retinoid status but not by dietary triglyceride intake.
Highlights
Hepatic stellate cells store the majority of the liver's retinoid reserves as retinyl esters in stellate cell lipid droplets
Oace taken up by the parenchymal cells, dietary retinoids are transferred to the stellate cells for storage [8, 10, 11].Studies from our laboratory suggest that chylomicron retinyl ester is not transferred directly from parenchymal to stellate cells without first undergoing hydrolysis to Abbreviations: cellular retinoic acidbinding protein (CRABP), cellular retinoic acid-binding protein; cellular retinolbinding protein (CRBP),cellular retinol-binding protein; HPLC,high performance liquid chromatography; RBP.retinol-binding protein; PBS,phosphate-buffered saline
T h e high retinol diet group, which was provided 10-fold the amount of retinol necessary to maintain normal vitamin A status, was found to have significantly elevated hepatic total retinol levels over the control diet group (Table 2). These rats showed no clinical signs of vitamin A toxicityand had normal serum retinol levels (Table 1) without retinyl esters being observed in the serum
Summary
Hepatic stellate cells store the majority of the liver's retinoid (vitamin A) reserves as retinyl esters in stellate cell lipid droplets. Control stellate cell lipid droplets had the following mean percent lipid composition: 39.5% retinyl ester; 31.7% triglyceride; 15.4%cholesteryl ester; 4.7% cholesterol; 6.3% phospholipids; and 2.4% free fatty acids. Low and high triglyceride groups were similar to controls in both stellate cell lipid content and the composition of the stellate cell lipid droplets. Oace taken up by the parenchymal cells, dietary retinoids are transferred to the stellate cells for storage [8, 10, 11].Studies from our laboratory suggest that chylomicron retinyl ester is not transferred directly from parenchymal to stellate cells without first undergoing hydrolysis to Abbreviations: CRABP, cellular retinoic acid-binding protein; CRBP,cellular retinol-binding protein; HPLC,high performance liquid chromatography; RBP.retinol-binding protein; PBS,phosphate-buffered saline. Retinol [11].T h e stellate cells are known to be the main storage site of retinoids in the liver [12,13,14,15]; stellate cells are highly enriched in both cellular retinolbinding protein (CRBP) and cellular retinoic acidbinding protein (CRABP), and in the enzymes that synthesizeand hydrolyze retinyl esters (acyl-CoA:retinol acyltransferase and retinyl palmitate hydrolase) [13, 14, 16]
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