MBX-102JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation
Joint Authors
Lee, Paul
Clemens, L. Edward
Clarke, Holly J.
Pandey, Bindu
Chandalia, Apurva
Vicena, Vic
Gregoire, Francine M.
Lavan, Brian E.
Source
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-04-23
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
MBX-102/JNJ-39659100 (MBX-102) is a selective, partial PPAR-γ agonist that lowers glucose in the absence of some of the side effects, such as weight gain and edema, that are observed with the TZDs.
Interestingly MBX-102 also displays pronounced triglyceride lowering in preclinical rodent models and in humans.
Although in vitro reporter gene studies indicated that MBX-102 acid is a highly selective PPAR-γ agonist that lacks PPAR-α activity, we sought to determine if PPAR-α activation in vivo could possibly contribute to the triglyceride lowering abilities of MBX-102.
In vivo studies using ZDF and ZF rats demonstrated that MBX-102 lowered plasma triglycerides.
However in ZF rats, MBX-102 had no effect on liver weight or on hepatic expression levels of PPAR-α target genes.
Further in vitro studies in primary human hepatocytes supported these findings.
Finally, the ability of MBX-102 to lower triglycerides was maintained in PPAR-α knockout mice, unambiguously establishing that the triglyceride lowering effect of MBX-102 is PPAR-α independent.
The in vivo lipid lowering abilities of MBX-102 are therefore mediated by an alternate mechanism which is yet to be determined.
American Psychological Association (APA)
Chandalia, Apurva& Clarke, Holly J.& Clemens, L. Edward& Pandey, Bindu& Vicena, Vic& Lee, Paul…[et al.]. 2009. MBX-102JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation. PPAR Research،Vol. 2009, no. 2009, pp.1-12.
https://search.emarefa.net/detail/BIM-492131
Modern Language Association (MLA)
Chandalia, Apurva…[et al.]. MBX-102JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation. PPAR Research No. 2009 (2009), pp.1-12.
https://search.emarefa.net/detail/BIM-492131
American Medical Association (AMA)
Chandalia, Apurva& Clarke, Holly J.& Clemens, L. Edward& Pandey, Bindu& Vicena, Vic& Lee, Paul…[et al.]. MBX-102JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation. PPAR Research. 2009. Vol. 2009, no. 2009, pp.1-12.
https://search.emarefa.net/detail/BIM-492131
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-492131