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Volume 272, Number 13,
Issue of March 28, 1997
pp. 8830-8835
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Uptake of Long Chain Free Fatty Acids Is Selectively
Up-regulated in Adipocytes of Zucker Rats with Genetic Obesity and
Non-insulin-dependent Diabetes Mellitus
(Received for publication, October 2, 1996, and in revised form, January 10, 1997)
Paul D.
Berk
§
,
Sheng-Li
Zhou
,
Chih-Li
Kiang
,
Decherd
Stump
,
Michael
Bradbury
and
Luis M.
Isola
From the Departments of Medicine (Divisions of Liver
Diseases and Hematology) and § Biochemistry,
Mount Sinai School of Medicine, New York, New York 10029
To examine whether fatty acid transport is
abnormal in obesity, the kinetics of [3H]oleate
uptake by hepatocytes, cardiac myocytes, and adipocytes from adult male
Wistar (+/+), Zucker lean (fa/+) and fatty
(fa/fa), and Zucker diabetic fatty (ZDF) rats
were studied. A tissue-specific increase in oleate uptake was found in
fa/fa and ZDF adipocytes, in which the
Vmax was increased 9-fold (p < 0.005) and 13-fold (p < 0.001), respectively. This
increase greatly exceeded the 2-fold increase in the surface area of
adipocytes from obese animals, and did not result from
trans-stimulation secondary to increased lipolysis. Adipocyte tumor
necrosis factor- mRNA levels, assayed by Northern hybridization,
increased in the order +/+ < fa/fa < ZDF. Oleate uptake was also studied in adipocytes from
20-24-day-old male +/+, fa/+, and fa/fa
weanlings. These animals were not obese, and had equivalent plasma
fatty acid and glucose levels. Tumor necrosis factor- mRNA
levels in +/+ and fa/fa cells also were similar.
Nevertheless, Vmax was increased 2.9-fold
(p < 0.005) in fa/fa compared +/+ cells.
These studies indicate 1) that regulation of fatty acid uptake is
tissue-specific and 2) that up-regulation of adipocyte fatty acid
uptake is an early event in Zucker fa/fa rats. These
findings are independent of the role of any particular fatty acid
transporter. Adipocyte mRNA levels of three putative transporters,
mitochondrial aspartate aminotransferase, fatty acid translocase, and
fatty acid transporting protein (FATP) were also determined;
mitochondrial aspartate aminotransferase and FATP mRNAs correlated
strongly with fatty acid uptake.

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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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