Increased Fatty Acid Uptake and Altered Fatty Acid Metabolism in Insulin-Resistant Muscle of Obese Zucker Rats

Increased Fatty Acid Uptake and Altered Fatty Acid Metabolism in Insulin-Resistant Muscle of Obese Zucker Rats Lorraine Patricia Turcotte , Jason Richard Swenberger , Michelle Zavitz Tucker and Alice Jane Yee Department of Kinesiology and University of Southern California Diabetes Center, University of Southern California, Los Angeles, Califonia Abstract Altered muscle fatty acid (FA) metabolism may contribute to the presence of muscle insulin resistance in the genetically obese Zucker rat. To determine whether FA uptake and disposal are altered in insulin-resistant muscle, we measured palmitate uptake, oxidation, and incorporation into di- and triglycerides in isolated rat hindquarters, as well as muscle plasma membrane fatty acid–binding protein (FABP PM ) content of lean ( n = 16, fa /+) and obese ( n = 15, fa / fa ) Zucker rats (12 weeks of age). Hindquarters were perfused with 7 mmol/l glucose, 1,000 μmol/l albumin-bound palmitate, and albumin-bound [1- 14 C]palmitate at rest (no insulin). Glucose uptake was 42% lower in the obese than in the lean rats and indicated the presence of muscle insulin resistance. Fractional and total rates of palmitate uptake were 42 and 74% higher in the obese than in the lean rats and were associated with higher muscle FABP PM content ( r 2 = 0.69, P < 0.05). The percentage of palmitate oxidized was not significantly different between groups. FA disposal to storage was altered according to fiber type. When compared with lean rats, the rate of triglyceride synthesis in red muscle was 158% higher in obese rats, and the rate of palmitate incorporation into diglycerides in white muscle was 93% higher in obese rats. Pre- and postperfusion muscle triglyceride levels were higher in both red and white muscles of the obese rats. These results show that increased FA uptake and altered FA disposal to storage may contribute to the development of muscle insulin resistance in obese Zucker rats. Footnotes Address correspondence and reprint requests to Lorraine P. Turcotte, Ph.D., Department of Kinesiology, University of Southern California, 3560 Watt Way, PED 107, Los Angeles, CA 90089. E-mail: turcotte{at}usc.edu . Received for publication 21 September 2000 and accepted in revised form 5 March 2001. CM, crude membrane; DGAT, diacylglycerol acyltransferase; FA, fatty acid; FABP PM , fatty acid–binding protein; FAT, fatty acid transporter; FFA, free fatty acid; GPAT, glycerol-3-phosphate acyltransferase; PM, plasma membrane; TBST, Tris-