Increased fatty acid uptake and altered fatty acid metabolism in insulin-resistant muscle of obese Zucker rats

Altered muscle fatty acid (FA) metabolism may contribute to the presence of muscle insulin resistance in the genetically obese Zucker rat. To determin e whether FA uptake and disposal are altered in insulin-resistant muscle, w e measured palmitate uptake, oxidation, and incorporation into di- and trig lycerides in isolated rat hindquarters, as well as muscle plasma membrane f atty acid-binding protein (FABP(PM)) content of lean (n = 16, f alpha/+) an d obese (n = 15,f alpha /f alpha) Zucker rats (12 weeks of age). Hindquarte rs were perfused with 7 mmol/l glucose, 1,000 mu mol/l albumin-bound palmit ate, and albumin-bound [1-C-14]palmitate at rest (no insulin). Glucose upta ke was 42% lower in the obese than in the lean rats and indicated the prese nce of muscle insulin resistance. Fractional and total rates of palmitate u ptake were 42 and 74% higher in the obese than in the lean rats and were as sociated with higher muscle FAB(PM), content (r(2) = 0.69, P < 0.05). The p ercentage of palmitate oxidized was not significantly different between gro ups. FA disposal to storage was altered according to fiber type. When compa red with lean rats, the rate of triglyceride synthesis in red muscle was 15 8% higher in obese rats, and the rate of palmitate incorporation into digly cerides in white muscle was 93% higher in obese rats. Pre- and postperfusio n muscle triglyceride levels mere higher in both red and white muscles of t he obese rats. These results show that increased FA uptake and altered FA d isposal to storage may contribute to the development of muscle insulin resi stance in obese Zucker rats.