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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 Dagger § , Sheng-Li Zhou Dagger , Chih-Li Kiang Dagger , Decherd Stump Dagger , Michael Bradbury Dagger and Luis M. Isola par

From the Departments of Medicine (Divisions of Dagger  Liver Diseases and par  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-alpha 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-alpha 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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