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Saturated- And N-6 Polyunsaturated-Fat Diets Each Induce Ceramide Accumulation In Mouse Skeletal Muscle: Reversal And Improvement Of Glucose Tolerance By Lipid Metabolism Inhibitors, G Frangioudakis, J Garrard, K Raddatz, J L. Nadler, Todd W. Mitchell, Carsten Schmitz-Peiffer

Faculty of Health and Behavioural Sciences - Papers (Archive)

Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg · d), or MYR …