Conjugated linoleic acid (CLA) isomers have been reported to reduce body weight and beneficially affect glucose metabolism in animals, but the results are inconsistent and seem to depend on animal model and type of CLA isomer. In the present study, feeding male Zucker fa/fa rats diets supplemented with 1% trans-10, cis-12-CLA for 10 d reduced the liver TAG content without improving the overall adiposity, and enhanced hepatic mitochondrial and peroxisomal beta-oxidation. The increased carnitine palmitoyltransferase (CPT)-I activity and mRNA level as well as the increased n-3:n-6 PUFA ratio in liver suggest that trans-10, cis-12-CLA increased the hepatic beta-oxidation by stimulation of PPARalpha. The reduced hepatic TAG content may be partly due to lower activity of stearoyl-CoA desaturase, as the ratios of 18 : 1n-9:18 : 0 and 16 : 1n-7:16 : 0 were reduced in liver. Trans-10, cis-12-CLA increased the CPT-I mRNA in retroperitoneal white adipose tissue (WAT), and increased uncoupling protein-2 mRNA in epididymal and inguinal WAT depots. Leptin mRNA level was decreased in all examined WAT depots, implying reduced insulin sensitivity. The resistin mRNA level was increased in all WAT depots, whereas adiponectin mRNA was reduced in inguinal and retroperitoneal WAT. The present results suggest that dietary supplementation with trans-10, cis-12-CLA may increase the catabolism of lipids in liver and adipose tissue. Moreover, we provide new data suggesting that trans-10, cis-12-CLA modulates the expression of resistin and adiponectin inversely in adipose tissue. Hence, the present results suggest that trans-10, cis-12-CLA may have some beneficial effects on lipid metabolism and adiposity but possibly reduces insulin sensitivity.