Metabolism of fenbufen by cultured 3T3-L1 adipocytes: synthesis and metabolism of xenobiotic glycerolipids.
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.
Dodds
P F
PF
Department of Biological Sciences, University of London, Wye, Ashford, Kent, United Kingdom.
Chou
S C
SC
Ranasinghe
A
A
Coleman
R A
RA
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002855:Chromatography, Thin Layer; D005989:Glycerides / Q000378:metabolism; D050356:Lipid Metabolism; D013058:Mass Spectrometry; D051379:Mice; D010654:Phenylbutyrates / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
D005989:Glycerides; D010654:Phenylbutyrates; D015262:Xenobiotics; C010725:fenbufen