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In two studies, mice were fed diets containing either individual conjugated linoleic acid (CLA) isomers or a mixture of isomers in the presence or absence of dietary essential fatty acids. Mice fed the C18:2 Δ10,12 CLA isomer lost as much body fat as mice fed a mixture of isomers. This effect was not observed when the mice were fed the C18:2 Δ9,11 isomer or when feed intake was restricted. The loss of body fat 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. Understanding the mechanism by which CLA causes body fat loss, in pigs as well as mice, will allow for greater regulation of body fat content.