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Molecular Biology Reports

, Volume 42, Issue 7, pp 1225–1232 | Cite as

Inhibition of MMP-13 prevents diet-induced obesity in mice and suppresses adipogenesis in 3T3-L1 preadipocytes

  • Chia-Li M. Shih
  • Kolapo M. AjuwonEmail author
Article

Abstract

Adipose tissue remodeling by the matrix metalloproteases (MMPs) is critical for tissue hypertrophy and obesity. MMP-13 is an important protein that is highly expressed in adipose tissue but whose potential role in adipose tissue expansion is poorly characterized. We investigated the effect of pharmacological inhibition of MMP-13 with a selective inhibitor, CP-544439, on adipose tissue mass in mice on a high fat diet, and determined the effect of the inhibitor during in vitro adipocyte differentiation of 3T3-L1 cells. CP-544439 was administered for 6 weeks to mice on a high fat diet. Body adiposity and glucose tolerance was determined. Differentiating 3T3-L1 adipocytes were also treated with the inhibitor for a maximum of 8 days and adipogenesis assessed. Treatment of mice with the inhibitor resulted in reduction in body adiposity and improvement in glucose clearance. Histological examination of epididymal adipose showed reduced adipocyte hypertrophy accompanied by increased staining for collagen in the inhibitor treated mice. Treatment of differentiating 3T3-L1 cells with the inhibitor resulted in reduced adipocyte differentiation. Knockdown of MMP-13 using small interfering RNA in differentiating 3T3-L1 cells reduced adipocyte differentiation indicated by reduced expression of PPARγ. These results suggest that MMP-13 may play a major role in adipose development and its inhibition could be a potential strategy to prevent obesity.

Keywords

Extracellular matrix MMP-13 Collagen adipose 

Notes

Acknowledgments

This work was supported in part by a Purdue Agricultural Research Assistantship to CMS. We acknowledge the generous donation of CP-54439 by Pfizer.

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Department of Animal SciencesPurdue UniversityWest LafayetteUSA

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