Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPAR gamma). PPAR gamma is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPAR gamma. However, the mechanism by which the alkyl-LPA-PPAR gamma axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPAR gamma activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPAR gamma 1 mRNA is more abundant than PPAR gamma 2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 mu M) significantly activated PPAR gamma and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPAR gamma and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance. (C) 2013 Elsevier Inc. All rights reserved.