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Peroxisome proliferator-activated receptor delta-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 beta/delta (PPARdelta) 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 PPARdelta 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 PPARdelta could be envisioned as a useful strategy against human metabolic syndrome and related diseases.
AuthorsWei Chen, Li-Li Wang, Hong-Ying Liu, Long Long, Song Li
JournalBasic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 103 Issue 3 Pg. 240-6 (Sep 2008) ISSN: 1742-7843 [Electronic] England
PMID18684227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Glucose
  • Cholesterol, HDL
  • Fatty Acids
  • GW 501516
  • Insulin
  • Leptin
  • PPAR delta
  • Thiazoles
  • Sodium Glutamate
Topics
  • Animals
  • Animals, Newborn
  • Blood Glucose (analysis)
  • Cholesterol, HDL (blood)
  • Dyslipidemias (prevention & control)
  • Fatty Acids (metabolism)
  • Gene Expression
  • Insulin (blood)
  • Insulin Resistance
  • Leptin (blood)
  • Metabolic Syndrome (chemically induced, metabolism, prevention & control)
  • Mice
  • Mice, Obese
  • Oxidation-Reduction
  • PPAR delta (agonists)
  • Sodium Glutamate
  • Thiazoles (pharmacology, therapeutic use)

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