Hepatic gene expression and fatty acid composition suggested enhanced hepatic de novo lipogenesis without an increase in expression of gluconeogenic genes. Unexpectedly, despite being insulin resistant, mice fed t10c12-CLA had normal levels of blood glucose, without signs of impaired glucose clearance. Hepatic steatosis and the disappearance of adipose tissue after t10c12-CLA feeding was associated with elevated plasma insulin levels and insulin resistance, compared to mice fed a control diet or c9t11-CLA diet. This rebound was apparently due to a massive accumulation of lipids in the liver, because adipose tissue depots were visually undetectable. However, 7 days after starting the t10c12-CLA diet, we observed a dramatic reduction in fat mass measured by NMR spectroscopy, which interestingly rebounded by 38 days. Diets containing c9t11-CLA had minimal impact on the endpoints studied. We fed 8 week-old C57Bl/6J male mice with low fat diets (10.5% Kcal from fat) containing 0.8% t10c12-CLA or c9t11-CLA for 9 or 38 days. Because of the reported adverse effects of CLA on insulin sensitivity in some mouse studies, we sought to compare the impact of dietary t10c12-CLA and c9t11-CLA on liver, adipose tissue, and systemic metabolism of adult lean mice. Cistrans isomerism is a common occurrence in substituted cycloalkanes and in many cyclic biological molecules. Mixtures of the two major conjugated linoleic acid (CLA) isomers trans-10, cis-12-CLA and cis-9, trans-11-CLA are used as over the counter supplements for weight loss. The prexes cis- (Latin on the same side) and trans- (Latin across) are used to distinguish between them.