The PPARδ agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells

Abstract 

Peroxisome proliferator-activated receptor-delta (PPARδ) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARδ agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1α and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARδ agonists in skeletal muscle.

Abbreviations: PPAR, peroxisome proliferator-activated receptor, PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator 1α, CPT-1, carnitine palmitoyl-transferase-1, GW, GW501516

Keywords: PPARβ/δ, GW501516, Glucose, Insulin, Metabolism