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Molecular and Cellular Biology, March 2009, p. 1575-1591, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01300-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI{triangledown} ,{dagger}

Tayeba Khan,1 Eric S. Muise,2 Puneeth Iyengar,1,{ddagger} Zhao V. Wang,3 Manisha Chandalia,4 Nicola Abate,4 Bei B. Zhang,5 Paolo Bonaldo,6 Streamson Chua,7 and Philipp E. Scherer3,8*

Department of Cell Biology,1 Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461,7 Departments of Molecular Profiling,2 Metabolic Disorders, Merck Research Laboratories, Rahway, New Jersey 07065,5 Departments of Internal Medicine,3 Cell Biology, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8549,8 Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas 75390,4 Department of Histology, Microbiology & Medical Biotechnologies, University of Padova, Viale Giuseppe Colombo 3, I-35121 Padua, Italy6

Received 15 August 2008/ Returned for modification 29 October 2008/ Accepted 22 December 2008

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.

* Corresponding author. Mailing address: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8549. Phone: (214) 648-8715. Fax: (214) 648-8720. E-mail: Philipp.Scherer{at}utsouthwestern.edu

{triangledown} Published ahead of print on 29 December 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Division of Radiation Oncology, UT MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 97, Houston, TX 77030.

Molecular and Cellular Biology, March 2009, p. 1575-1591, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01300-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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