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

Abstract

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 VAsufficient 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 Ͻ 0.001). This reduction was accompanied by a 68% increase in hepatic retinol concentration by 7 days ( P Ͻ 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 Ͻ 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. -Gieng, S. H., J. Raila, and F. J. Rosales. Accumulation of retinol in the liver after prolonged hyporetinolemia in the vitamin A-sufficient rat. J. Lipid Res. 2005. 46: 641-649.

Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats

“…The possible underlying mechanisms include the following: 1) impaired absorption or cleavage of dietary proformed carotenoids or preformed VA (6); 2) increased utilization of VA subsequent to its immune-potentiating role during infections (7); 3) increased glomerular filtration followed by an impaired reabsorption in the proximal tubule, leading to retinol and retinol binding protein (RBP) being excreted in urine (8); and 4) reduced hepatic synthesis of RBP and decreased secretion of retinol into plasma (9,10). We have shown previously that inflammation induced with lipopolysaccharide (LPS) or recombinant human interleukin-6 (rhIL-6) decreases the availability of RBP and increases the concentrations of hepatic retinol or retinyl esters (9,11). However, the effect(s) of this decrease in RBP and the increase in hepatic VA on the kinetics and dynamics of whole-body retinol flux during inflammation has not been studied previously.…”

“…Trimethylmethoxyphenyl (TMMP)-retinol was a generous gift from Hoffmann-La Roche (Basel, Switzerland). [11, …”

“…At 0 and 21 days, additional rats were euthanized to determine baseline and perturbation liver VA concentrations (n 5 4/day). We selected LPS and rhIL-6 at these doses because in our previous experiments (9, 11) we demonstrated that these doses induced inflammation without septicemia or renal failure, and they allowed us to examine the effects of the acute-phase response of inflammation on the distribution of VA and RBP in various tissues (9,11). Additionally, rhIL-6 induced and maintained the acute-phase response of inflammation for up to 7 days without causing metabolic alterations or reducing food intake (11).…”

“…Rats received orally [11, H(N)]retinol ([ 3 H]VA; day 0), and inflammation was induced on day 21 with lipopolysacchride (LPS) for 3 days (n 5 5) or recombinant human interleukin-6 (rhIL-6) for 7 days (n 5 5). Both the fraction of [ 3 H]VA and retinol concentrations in plasma were reduced significantly by LPS or rhIL-6.…”

Vitamin A intake and infection are associated with plasma retinol among pre-school children in rural Zambia

“…Acute infections are associated with increased urinary excretion of vitamin A (3,4) and recent fever is associated with decreased absorption and retention of a vitamin A dose (5) . In addition, current infection reduces plasma retinol concentration by reducing hepatic synthesis and circulation of retinol-binding protein (6) . As a result, the prevalence of VAD is overestimated in populations where infections are prevalent (7) .…”