Retinol release by activated rat hepatic lipocytes: regulation by Kupffer cell-conditioned medium and PDGF

In normal liver, lipocytes are the principal reservoir for retinoids, which are stored as retinyl esters. In liver injury, lipocytes activate into myofibroblast-like cells, which lack retinoid. We examined mechanisms of retinoid loss using a culture model in which lipocyte activation is provoked by exposure to Kupffer cell-conditioned medium (KCM) (S.L. Friedman and M. J. P. Arthur, J. Clin. Invest. 84: 1780-1785, 1989). In lipocytes exposed to KCM, there was approximately 11-fold more retinol in medium than in untreated cells, without release of retinyl esters. Both bile salt-dependent and -independent retinyl ester hydrolase was entirely intracellular, suggesting that the increase in retinol was due to intracellular hydrolysis; activity of bile salt-independent hydrolase was increased in KCM-treated lipocytes. Release of retinol was serum dependent and inhibited 40% by antibodies to platelet-derived growth factor (PDGF). The addition of 10 nM PDGF to serum-free KCM also induced retinol release. Lipocyte expression of mRNAs for cellular retinol-binding protein, retinoic acid receptor (RAR)-alpha, and RAR-beta was unchanged after exposure to KCM. In summary, activation of cultured lipocytes by KCM is accompanied by serum- and PDGF-dependent release of retinol; a similar mechanism may underlie retinoid loss by activated lipocytes in vivo.