10, 12 CLA promotes insulin resistance by antagonizing PPARγ

10,12 CLA is a naturally occurring dietary trans fatty acid reported to promote weight loss. Despite carrying significantly less fat than control mice, mice consuming 10,12 CLA do not show improved glucose metabolism. PPARγ is abundantly expressed in adipose tissue, where it contributes to whole-body glucose homeostasis. Congruent with the loss of fat mass, 10,12 CLA-supplemented mice have reduced PPARγ gene expression. We therefore hypothesize that 10,12 CLA contributes to insulin resistance by attenuating PPARγ activity. Dr. den Hartigh will examine cellular mechanisms by which 10,12 CLA could attenuate PPARγ expression and/or activity, and determine if a potent PPARγ agonist, rosiglitazone, restores insulin sensitivity in mice.