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Abstract #1677

PPAR&[delta] Agonist Treatment Increases Skeletal Muscle Lipid Metabolism Without Altering Mitochondrial Coupling: An In Vivo Magnetic Resonance Spectroscopy Study

Yang D, Casey W, Olzinski A, Williams C, Lenhard S, Legos J, Hawk T, Jucker B, Sarkar S, Newsholme S
GlaxoSmithKline

PPAR&[delta] nuclear receptor activation results in activation of genes involved in skeletal muscle fatty acid oxidation and mitochondrial uncoupling. In present study, we examined the temporal and dose dependent response of a selective PPAR&[delta] agonist (GW610742X) treatment on intramyocellular lipid (IMCL) content and mitochondrial energy coupling efficiency rat hindlimb by in vivo MRS. There was a dose dependent decrease in soleus muscle IMCL/tCr ratio that was consistent with an increase in relative fat oxidation rate. However there was no alteration in hindlimb mitochondrial coupling efficiency measured as the ratio of unidirectional ATP synthesis to TCA cycle flux.