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

To examine whether fatty acid transport is abnormal in obesity, the ki netics of [H-3]oleate uptake by hepatocytes, cardiac myocytes, and adi pocytes from adult male Wistar (+/+), Zucker lean (fa/+) and fatty (fa /fa), and Zucker diabetic fatty (ZDF) rats were studied. A tissue-spec ific increase in oleate uptake was found in fa/fa and ZDF adipocytes, in which the V-max was increased 9-fold (p < 0.005) and 13-fold (p < 0 .001), respectively. This increase greatly exceeded the 2-fold increas e in the surface area of adipocytes from obese animals, and did not re sult from trans-stimulation secondary to increased lipolysis. Adipocyt e tumor necrosis factor-alpha mRNA levels, assayed by Northern hybridi zation, increased in the order +/+ < fa/fa < ZDF. Oleate uptake was al so studied in adipocytes from 20-24-day-old male +/+, fa/+, and fa/fa weanlings. These animals were not obese, and had equivalent plasma fat ty acid and glucose levels. Tumor necrosis factor-cy mRNA levels in +/ + and fa/fa cells also were similar. Nevertheless, V-max was increased 2.9-fold (p < 0.005) in fa/fa compared +/+ cells. These studies indic ate 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 puta tive transporters, mitochondrial aspartate aminotransferase, fatty aci d translocase, and fatty acid transporting protein (FATP) were also de termined; mitochondrial aspartate aminotransferase and FATP mRNAs corr elated strongly with fatty acid uptake.