The role of macrophage-derived MMP12 in diet-induced obesity

2008 2008

Other formats:

This graduate work is not available to view or purchase.

Abstract (summary)

Background. Macrophages accumulation in adipose tissue of obese mice is accompanied by increased expression of pro-inflammatory adipokines, cytokines and chemokines, leading to the proposal that macrophages are of central importance in the systemic inflammation associated with obesity. Matrix metalloproteinases (MMPs) are implicated in cytokine and chemokine release, matrix remodeling, and the release of inflammatory mediators. Levels of macrophage metalloelastase (MMP-12, a macrophage-specific enzyme) increase dramatically in the stromovascular fraction of adipose tissue when mice are fed a high-fat diet. We used mice deficient in MMP-12 (Mmp12-/- ) to investigate the role of macrophages in diet-induced obesity.

Methods and results. C57BL/6J (WT) and Mmp12 -/- mice were fed a high or low fat diet (Research Diets, with 60% or 12% Kcal fat) for 10 weeks after weaning. Mmp12 -/- mice fed a high-fat diet gained markedly more weight than did WT mice (43.9±0.8 vs 35.2±0.6 g, p<0.01, n≥50/group); they also exhibited significantly more adipose tissue mass (43.0±1.6% vs 24.3±3.0%, p<0.05, n=4/group) and less lean mass (47.6±1.6% vs 63.1±2.4%, p<0.05, n=4/group) than WT mice. Although, diet-induced obese Mmp12-/- mice did not eat more than WT mice, they were less active than WT mice. Surprisingly, despite the increased weight gain, Mmp12-/- mice were not more insulin resistant than WT mice. Furthermore, levels of circulating cytokines (IL-6, MCP-1, Resistin, and tPAI-1) and inflammatory cytokines in adipose tissue (IL-6, MCP-1, and TNF-α) were similar in both diet-induced obese Mmp12-/- and WT mice. However, there were increased macrophages in adipose tissue in diet-induced obese Mmp12-/- mice compared with WT mice. Levels of markers in adipose tissue for alternatively activated macrophages were significantly higher in Mmp12-/- than WT mice.

Conclusion. Our observations indicate that MMP-12 expressed by macrophages plays previously unsuspected roles in adipose tissue accumulation, a shift of adipose tissue macrophage polarization, and systemic inflammation during diet-induced obesity.

Indexing (details)

0433: Physiology
0570: Nutrition
0766: Epidemiology
Identifier / keyword
Health and environmental sciences; Biological sciences; Adipose tissue; MMP12; Obesity
The role of macrophage-derived MMP12 in diet-induced obesity
Lee, Jung-Ting
Number of pages
Publication year
Degree date
School code
DAI-B 70/01, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
Kirk, Elizabeth A.
University of Washington
University location
United States -- Washington
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.