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PPAR Research
Volume 2009 (2009), Article ID 706852, 12 pages
Research Article

MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR- 𝛾 Agonist Lowers Triglyceride Independently of PPAR- 𝛼 Activation

1Department of Biology, Metabolex, Inc., 3876 Bay Center Place, Hayward, CA 94545, USA
2Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA

Received 3 December 2008; Accepted 7 February 2009

Academic Editor: Anna Tsantili-Kakoulidou

Copyright © 2009 Apurva Chandalia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.