C333H, a novel PPARalpha/gamma dual agonist, has beneficial effects on insulin resistance and lipid metabolism.
OBJECTIVE
To examine the effects of novel peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist C333H on insulin resistance and lipid metabolism.


METHODS
An established dual-luciferase reporter gene assay system was used in vitro to test the activity of C333H with respect to the transcription of human PPARalpha and PPARgamma. A preadipocyte differentiation assay and reverse transcription-polymerase chain reaction were used to detect the functional activities of C333H. In db/db mice, the effects of C333H were investigated with respect to lowering of blood glucose and lipid levels.


RESULTS
C333H was determined to be a novel PPARalpha/gamma dual agonist because it strongly induced luciferase activity on human PPARalpha and PPARgamma, promoting the differentiation of preadipocytes to adipocytes, and functioning in upregulating the expression of some glucose and lipid metabolic target genes of the PPAR. In addition, C333H efficiently reduced blood lipid and glucose concentrations in db/db diabetic mice.


CONCLUSIONS
C333H has dual action on both PPARalpha and PPARgamma, and might be of interest for the amelioration of lipid metabolic disorders and insulin resistance associated with type 2 diabetes.
Xu
Cheng
C
Institute of Pharmacology and Toxicology, Beijing 100850, China.
Wang
Li-li
LL
Liu
Hong-ying
HY
Zhou
Xing-bo
XB
Cao
Ying-lin
YL
Li
Song
S
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005663:Furans / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology*; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; C513069:C333H compound; D005230:Fatty Acids, Nonesterified; D005663:Furans; D051275:Glucose Transporter Type 4; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase