Metabolic effects of fatty acid bearing albumin on a proximal
tubule cell line..
Schreiner, Mark E. Thomas Aubrey R. Morrison & George F.
Renal Division, Washington University School of Medicine, St Louis,
Missouri, 63110, USA, CV Therapeutics, Inc., 3172 Porter Drive, Palo
Alto, CA, 94304, USA.
APStracts 2:0007F, 1995.
In glomerular disease fatty acids carried on albumin are taken up by
the proximal tubule with filtered albumin. We postulate that the
fatty acids carried on filtered albumin could contribute to the
deleterious effects of proteinuria. The effects of fatty acid-albumin
complexes on lipid metabolism have been studied in Opossum kidney
(OK) cells, a proximal tubule cell line. OK cells transported two
-thirds of 14C-palmitate-albumin (5 mg/ml) intracellularly within 16
hours. 14C-palmitate-albumin was distributed into
phosphatidylcholines, phosphatidylinositols, tri- and diglycerides.
14C-labelled unsaturated fatty acid-albumins (oleate, linoleate and
arachidonate) showed preferential incorporation into triglycerides,
with lesser incorporation into phospholipids. Studies of total lipid
pools showed that fatty acid-albumin uptake produced a particularly
marked increase in total triglyceride levels (some 10-fold). Oil Red
O staining of OK cells cultured with oleate-albumin showed a marked
increase in intracellular lipid droplets, compared to cells cultured
with delipidated albumin, consistent with triglyceride accumulation.
Less than 1% of 14C-palmitate taken up was isolated as intracellular
free fatty acid. Less than 5% of 14C-palmitate internalized was
oxidized to 14CO2. Different fatty acids, when taken up by the OK
cell, have distinct metabolic fates. Each fatty acid is incorporated
in a characteristic fashion into certain complex lipids, possibly
dependent on the presence or absence of double bonds. We propose that
this may have functional consequences for the proximal tubule in the
human nephrotic syndrome.
Received 17 March 1994; accepted in final form 30 January 1995.
APS Manuscript Number F93-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.