Journal of Lipid Research, Vol 36, 2493-2503, Copyright © 1995 by Lipid Research, Inc.
Metabolism of fenbufen by cultured 3T3-L1 adipocytes: synthesis and metabolism of xenobiotic glycerolipids
PF Dodds, SC Chou, A Ranasinghe and RA Coleman
Department of Biological Sciences, University of London, Wye, Ashford, Kent, United Kingdom.
The storage of xenobiotic compounds as glycerolipids and their subsequent
mobilization was studied using fenbufen and differentiated 3T3-L1 cells in
culture. Fenbufen was taken up from the incubation medium and incorporated
into triacylglycerol, diacylglycerol, and phospholipids. The
triacylglycerol was susceptible to digestion by pancreatic lipase. The
xenobiotic phospholipid contained three species, one of which behaved as
fenbufenoyl phosphatidylcholine as judged by TLC, HPLC, choline analysis,
and mass spectroscopy. After incubation with radioactive fenbufen for 18 h,
the cells were transferred to a chase medium where radioactivity was lost
from the cells and appeared in the medium. The rate was three times higher
when 10 microM isoproterenol was present; insulin had no effect.
Non-esterified fenbufen and analogues of mono- and di-acylglycerol were
secreted. Monofenbufenoylglycerol was characterized by its ability to be
used as a substrate by purified monoacylglycerol acyltransferase. When
oleic acid was used in place of fenbufen, the majority of the radioactivity
released in a chase experiment was the non-esterified acid (over 90%) and
neither mono- nor di-acylglycerol was detected. These data indicate that
3T3-L1 adipocytes can synthesize fenbufen-containing lipids and release
them into the medium on hormonal stimulation. The secretion of mono- and
di-acylglycerols may have unforeseen pharmacological or toxicological
implications.
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