Obesity-induced remodeling of the adipose tissue elastin network is independent of the metalloelastase MMP-12

Abstract

The extracellular matrix (ECM) plays important roles in maintaining adequate adipose tissue function and in metabolic regulation. Here we have examined the organization of a relatively unexplored adipose tissue ECM component, elastin and its response to diet induced obesity in mice. Additionally, we have explored the regulation and requirement of macrophage metalloelastase, MMP-12, in adipose tissue ECM remodeling in obesity. In visceral fat depots, elastin fibers form a mesh-like net that becomes denser with diet-induced obesity. In contrast, the elastin fibers in subcutaneous adipose depots are more linear in organization, and are tightly associated with adipose tissue macrophages (ATMs). We found that Mmp12 is produced predominantly by ATMs and can be induced with both short- and long-term high fat diet challenge and rapid remodeling induced by lipolysis. This contrasts with Mmp14 and Timp1 which are further induced only after chronic obesity in non-ATM populations. We examined obese transgenic Mmp12^−/− mice and found an increase in gene expression of ECM genes with diet-induced obesity, but showed few significant differences in metabolic parameters, elastin matrix density, or in adipose tissue inflammation. Together, these studies reveal the architecture and diet-induced regulation of the elastin matrix and suggest that MMP-12 is not required for elastin matrix remodeling or for the metabolic dysfunction that occurs with obesity.

Keywords:

• adipose tissue fibrosis
• adipose tissue macrophages
• elastin
• extracellular matrix
• obesity

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgment

We thank Dr. Robert Mecham (Washington University in St. Louis) for providing elastin antibodies.

Funding

This work was carried out with support from grants from the NIH (DK090262 and DK092873) and the American Diabetes Association to C.N.L and an NIH Diversity Supplement for DK090262-S1 to GM-S. This work utilized Core Services from the Michigan Nutrition and Obesity Research Center supported by grant DK089503 of NIH to the University of Michigan. This work utilized the Microscopy Core of the Michigan Diabetes Research Center funded by NIH 2P30-DK20572 from the National Institute of Diabetes & Digestive & Kidney Diseases.