Effect of conjugated linoleic acid isomers on insulin resistance and mRNA levels of genes regulating energy metabolism in high-fat-fed rats

Objective: We investigated the effects of specific conjugated linoleic acid (CLA) isomers on glucose metabolism and insulin resistance and on mRNA levels of genes important in glucose and lipid metabolism. Methods: Sprague-Dawley rats were fed for 8 wk on a high-fat diet (45% kcal from fat) or one of three CLA- supplemented diets (1 % CLA) containing differing isomers of CLA, including a mixture of CLAs (CLA mix), cis-9, trans-11-CLA (C9,T11-CLA), or trans-10, cis-12-CLA (T10,C12-CLA). Results: Compared with the high-fat group, all the CLA groups had enhanced glucose tolerance. Insulin resistance index was significantly lower in the CLA-treated groups. No significant difference could be observed in the level of serum lipids between groups and in the activities of phosphoenolpyruvate carboxylase, glucose-6-phosphatase, and glucokinase. However, C9,T11-CLA and T10,C12-CLA significantly increased acyl coenzyme A oxidase mRNA in skeletal muscle. In addition, C9,T11-CLA increased hepatic acyl coenzyme A oxidase mRNA and skeletal muscle uncoupling protein-2 mRNA. The CLA mix showed intermediate effects on the levels of these genes. Conclusions: The addition of all types of CLA to Sprague-Dawley rats fed a-high-fat diet can decrease insulin resistance. Possible mechanisms are increased fat oxidation and energy expenditure by increasing acyl coenzyme A oxidase and uncoupling protein-2 mRNA in the liver and/or skeletal muscle. (C) 2004 Elsevier Inc. All rights reserved.