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In two studies mice were fed diets containing either a mixture of, or individual conjugated linoleic acid (CLA) isomers in the presence or absence of essential fatty acids. Mice fed the C18:2 Δ10,12 CLA isomer lost as much body fat as those fed a mixture of isomers. This effect was not caused by the C18:2 Δ9,11 isomer (predominant in beef) or by restricted feed intake. The loss was much greater in mice consuming an essential fatty acid deficient diet versus a control diet. This supports our hypothesis that for CLA to deplete body fat, it must first be metabolized in a manner similar to linoleic acid. Furthermore, we suggest that the loss of body fat may be mediated by metabolism of CLA to an isomer of arachidonic acid.