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The PPAR α / γ dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats
Author(s) -
Li PingPing,
Shan Song,
Chen YueTeng,
Ning ZhiQiang,
Sun SuJuan,
Liu Quan,
Lu XianPing,
Xie MingZhi,
Shen ZhuFang
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706745
Subject(s) - medicine , endocrinology , rosiglitazone , insulin resistance , nefa , dyslipidemia , triglyceride , insulin , glucose homeostasis , chemistry , diabetes mellitus , cholesterol
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 PPAR α . 2 Chiglitazar is a PPAR α / γ 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 PPAR α , CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats. 6 These data suggest that PPAR α / γ 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 PPAR γ agonists.British Journal of Pharmacology (2006) 148 , 610–618. doi: 10.1038/sj.bjp.0706745