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Journal of Lipid Research, Vol. 46, 641-649, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Accumulation of retinol in the liver after prolonged hyporetinolemia in the vitamin A-sufficient rat

Sin H. Gieng^*, Jens Raila and Francisco J. Rosales^1,*

^* Department of Nutritional Sciences, Pennsylvania State University, University Park, PA
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany

¹ To whom correspondence should be addressed. e-mail: fxr5{at}psu.edu

We assessed the effects of prolonged reduction of plasma retinol concentrations (hyporetinolemia) on the distribution of tissue vitamin A (VA) and of its active compounds using a model of continuous recombinant human interleukin-6 (rhIL-6) infusion via osmotic minipumps in VA-sufficient male rats. Plasma retinol and retinol-binding protein (RBP) concentrations remained decreased and lower in rhIL-6-treated rats compared with controls from 7.5 h throughout 7 days of infusion (P < 0.001). This reduction was accompanied by a 68% increase in hepatic retinol concentration by 7 days (P < 0.05). Hepatic and renal retinyl palmitate and retinoic acid concentrations did not change, and renal megalin content remained unchanged; hepatic RBP concentrations were 41% lower in rhIL-6-treated rats compared with controls (P < 0.05). These results indicate that instead of being lost, retinol accumulated in the liver during inflammation and that hyporetinolemia was attributable to a decrease in the availability of hepatic RBP. A plausible consequence of the effect of rhIL-6-induced hyporetinolemia is that by 7 days tissues that are dependent on plasma retinol may become deprived of VA.

These results have important implications in understanding the mechanism by which measles infection induces hyporetinolemia and VA deficiency of extrahepatic tissues.

Abbreviations: AGP, -1-acid glycoprotein; DAB, 3,3'-diaminobenzidine tetrahydrochloride; LPS, lipopolysaccharide; RBP, retinol-binding protein; rhIL-6, recombinant human interleukin-6; RID, radial immunodiffusion; SPE, solid-phase extraction; TBST, Tris-buffered saline containing Tween; TMMP, trimethylmethoxyphenyl; VA, vitamin A

Supplementary key words megalin • retinoic acid • retinol-binding protein • retinyl esters

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