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MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation
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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673481/ https://www.ncbi.nlm.nih.gov/pubmed/19404482 http://dx.doi.org/10.1155/2009/706852 |
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author | Chandalia, Apurva Clarke, Holly J. Clemens, L. Edward Pandey, Bindu Vicena, Vic Lee, Paul Lavan, Brian E. Gregoire, Francine M. |
author_facet | Chandalia, Apurva Clarke, Holly J. Clemens, L. Edward Pandey, Bindu Vicena, Vic Lee, Paul Lavan, Brian E. Gregoire, Francine M. |
author_sort | Chandalia, Apurva |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2673481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-26734812009-04-29 MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation Chandalia, Apurva Clarke, Holly J. Clemens, L. Edward Pandey, Bindu Vicena, Vic Lee, Paul Lavan, Brian E. Gregoire, Francine M. PPAR Res Research Article 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. Hindawi Publishing Corporation 2009 2009-04-23 /pmc/articles/PMC2673481/ /pubmed/19404482 http://dx.doi.org/10.1155/2009/706852 Text en Copyright © 2009 Apurva Chandalia et al. https://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Article Chandalia, Apurva Clarke, Holly J. Clemens, L. Edward Pandey, Bindu Vicena, Vic Lee, Paul Lavan, Brian E. Gregoire, Francine M. MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation |
title | MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation |
title_full | MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation |
title_fullStr | MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation |
title_full_unstemmed | MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation |
title_short | MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation |
title_sort | mbx-102/jnj39659100, a novel non-tzd selective partial ppar-γ agonist lowers triglyceride independently of ppar-α activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673481/ https://www.ncbi.nlm.nih.gov/pubmed/19404482 http://dx.doi.org/10.1155/2009/706852 |
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