Metabolic dysregulation and adipose tissue fibrosis: Role of collagen VI

Tayeba Khan, Eric S. Muise, Puneeth Iyengar, Zhao V. Wang, Manisha Chandalia, Nicola Abate, Bei B. Zhang, Paolo Bonaldo, Streamson Chua, Philipp E. Scherer

Research output: Contribution to journalArticle

548 Scopus citations

Abstract

Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.

Original languageEnglish (US)
Pages (from-to)1575-1591
Number of pages17
JournalMolecular and cellular biology
Volume29
Issue number6
DOIs
StatePublished - Mar 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Khan, T., Muise, E. S., Iyengar, P., Wang, Z. V., Chandalia, M., Abate, N., Zhang, B. B., Bonaldo, P., Chua, S., & Scherer, P. E. (2009). Metabolic dysregulation and adipose tissue fibrosis: Role of collagen VI. Molecular and cellular biology, 29(6), 1575-1591. https://doi.org/10.1128/MCB.01300-08