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

Am J Physiol. 1993 May;264(5 Pt 1):G947-52. doi: 10.1152/ajpgi.1993.264.5.G947.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Bile Acids and Salts / pharmacology
  • Blotting, Northern
  • Carboxylic Ester Hydrolases / metabolism
  • Cells, Cultured
  • Culture Media, Conditioned
  • Kinetics
  • Kupffer Cells / physiology*
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • Microsomes / drug effects
  • Microsomes / metabolism
  • Palmitic Acid
  • Palmitic Acids / metabolism
  • Platelet-Derived Growth Factor / pharmacology*
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Retinol-Binding Proteins / genetics
  • Retinol-Binding Proteins / metabolism
  • Retinol-Binding Proteins, Cellular
  • Vitamin A / analogs & derivatives
  • Vitamin A / metabolism*

Substances

  • Bile Acids and Salts
  • Culture Media, Conditioned
  • Palmitic Acids
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Cellular
  • Vitamin A
  • Palmitic Acid
  • Carboxylic Ester Hydrolases
  • retinyl esterase