The PPARalpha/gamma dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats.

Abstract

1. The aim of this study was to investigate the capacity of chiglitazar to improve insulin resistance and dyslipidemia in monosodium L-glutamate (MSG) obese rats and to determine whether its lipid-lowering effect is mediated through its activation of PPARalpha. 2. Chiglitazar is a PPARalpha/gamma dual agonist. 3. The compound improved impaired insulin and glucose tolerance; decreased plasma insulin level and increased the insulin sensitivity index and decreased HOMA index. Euglycemic hyperinsulinemic clamp studies showed chiglitazar increased the glucose infusion rate in MSG obese rats. 4. Chiglitazar inhibited alanine gluconeogenesis, lowered the hepatic glycogen level in MSG obese rats. Like rosiglitazone, chiglitazar promoted the differentiation of adipocytes and decreased the maximal diameter of adipocytes. In addition, chiglitazar decreased the fibrosis and lipid accumulation in the islets and increased the size of islets. 5. Chiglitazar reduced plasma triglyceride, total cholesterol (TCHO), nonesterified fatty acids (NEFA) and low density lipoprotein-cholesterol levels; lowered hepatic triglyceride and TCHO contents; decreased muscular NEFA level. Unlike rosiglitazone, chiglitazar showed significant increase of mRNA expression of PPARalpha, CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats. 6. These data suggest that PPARalpha/gamma coagonist, such as chiglitazar, affect lipid homeostasis with different mechanisms from rosiglitazone, chiglitazar may have better effects on lipid homeostasis in diabetic patients than selective PPARgamma agonists.

• Authors: Ping-Ping Li, Song Shan, Yue-Teng Chen, Zhi-Qiang Ning, Su-Juan Sun, Quan Liu, Xian-Ping Lu, Ming-Zhi Xie, Zhu-Fang Shen
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 148 Issue 5 Pg. 610-8 (Jul 2006) ISSN: 0007-1188 [Print] England
• PMID: 16751799 (Publication Type: Comparative Study, Evaluation Study, Journal Article)

Chemical References

• Blood Glucose
• Carbazoles
• Hypoglycemic Agents
• Lipids
• Liver Glycogen
• PPAR alpha
• PPAR gamma
• Propionates
• Pyrimidines
• Thiazolidinediones
• chiglitazar
• Rosiglitazone
• pirinixic acid
• Sodium Glutamate
• Pioglitazone

Topics

• Adipose Tissue (cytology, drug effects)
• Animals
• Blood Glucose (drug effects)
• Carbazoles (pharmacology)
• Disease Models, Animal
• Dyslipidemias (chemically induced, drug therapy)
• Gene Expression (drug effects)
• Gluconeogenesis (drug effects)
• Hypoglycemic Agents (therapeutic use)
• Insulin Resistance
• Lipids (analysis, blood)
• Liver (chemistry, drug effects)
• Liver Glycogen (analysis)
• Muscles (chemistry, drug effects)
• Obesity (chemically induced)
• PPAR alpha (agonists)
• PPAR gamma (agonists)
• Pancreas (cytology, drug effects)
• Pioglitazone
• Propionates (pharmacology)
• Pyrimidines (pharmacology)
• Rats
• Rats, Wistar
• Rosiglitazone
• Sodium Glutamate
• Thiazolidinediones (pharmacology)