The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) reduces body fat gain in animals and inhibits stearoyl-CoA desaturase (SCD) activity in 3T3-L1 adipocytes. To test whether CLA's body fat reduction is mediated by SCD1, wild-type and SCD1-null mice were fed diet supplemented with 0.2% trans-10,cis-12 (t10c12) CLA for 4 weeks. The t10c12 CLA-supplemented diet significantly reduced body fat mass in both wild type and SCD1-null mice. Similarly, t10c12 CLA diet decreased blood triglyceride and free fatty acid levels regardless of SCD1 genotypes. Mice fed t10c12 CLA exhibited increased mRNA expression of fatty acid synthase and uncoupling protein 2 in both genotypes. Taken together, the effects of t10c12 CLA on reduction of body fat gain, blood parameters, and mRNA expression in both SCD1-null mice and wild-type mice were similar, indicating that the anti-obesity effect of t10c12 CLA may be independent of the effects of this CLA isomer on SCD1 gene expression and enzyme activity. (C) 2004 Elsevier Inc. All rights reserved.