title: 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.
authors.affiliation: Department of Pediatrics and Communicable Diseases; University of Michigan ; Ann Arbor, MI, USA ; Graduate Program in Cellular and Molecular Biology; University of Michigan ; Ann Arbor, MI, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Martinez-Santibanez
authors.affiliation: Department of Pediatrics and Communicable Diseases; University of Michigan ; Ann Arbor, MI, USA.
authors.forename: Kanakadurga
authors.initials: K
authors.lastname: Singer
authors.affiliation: Department of Pediatrics and Communicable Diseases; University of Michigan ; Ann Arbor, MI, USA.
authors.forename: Kae Won
authors.initials: KW
authors.lastname: Cho
authors.affiliation: Department of Pediatrics and Communicable Diseases; University of Michigan ; Ann Arbor, MI, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: DelProposto
authors.affiliation: Department of Pediatrics and Communicable Diseases; University of Michigan ; Ann Arbor, MI, USA.
authors.forename: Taleen
authors.initials: T
authors.lastname: Mergian
authors.affiliation: Department of Pediatrics and Communicable Diseases; University of Michigan ; Ann Arbor, MI, USA ; Graduate Program in Cellular and Molecular Biology; University of Michigan ; Ann Arbor, MI, USA.
authors.forename: Carey N
authors.initials: CN
authors.lastname: Lumeng
keywords: adipose tissue fibrosis; adipose tissue macrophages; elastin; extracellular matrix; obesity