Peroxisome proliferator-activated receptor δ-agonist, GW501516, ameliorates insulin resistance, improves dyslipidaemia in monosodium L-glutamate metabolic syndrome mice

Abstract

We evaluated the effects of GW501516, a specific peroxisome proliferator-activated receptor β/δ (PPARδ) agonist in metabolic syndrome mice, obtained by perinatal injection of monosodium l-glutamate, to investigate the efficacy of GW501516 against metabolic syndrome and the effectiveness of PPARδ activation as therapeutic target for metabolic syndrome. After 14 days treatment, GW501516 effectively improved the glucose intolerance, normalized the fasted blood glucose, and increased the serum high-density lipoprotein cholesterol (HDL-C) level. Postprandial blood glucose, serum insulin, leptin, free fatty acid (FFA) levels, and total cholesterol/HDL-C ratio were also significantly decreased. Moreover, semiquantitative reverse transcription-polymerase chain reaction results indicated that the above phenotypes might be due to (i) enhancement of fatty acid oxidation in muscle, adipose tissue and the liver; (ii) improvement of insulin-stimulated glucose transportation in skeletal muscle and adipose tissue; and (iii) reduced local glucocorticoid synthesis. Therefore, GW501516 could significantly ameliorate dyslipidaemia and insulin resistance in monosodium l-glutamate mice and activation of PPARδ could be envisioned as a useful strategy against human metabolic syndrome and related diseases. © 2008 The Authors.