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Diabetes. 2014 Jun;63(6):1920-32. doi: 10.2337/db13-1604. Epub 2014 Jan 23.

The extracellular matrix protein MAGP1 supports thermogenesis and protects against obesity and diabetes through regulation of TGF-β.

Author information

  • 1Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO clarissa.craft@wustl.edu.
  • 2Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO.
  • 3Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO.
  • 4Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO.
  • 5Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MODepartment of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO.

Abstract

Microfibril-associated glycoprotein 1 (MAGP1) is a component of extracellular matrix microfibrils. Here we show that MAGP1 expression is significantly altered in obese humans, and inactivation of the MAGP1 gene (Mfap2(-/-)) in mice results in adipocyte hypertrophy and predisposition to metabolic dysfunction. Impaired thermoregulation was evident in Mfap2(-/-) mice prior to changes in adiposity, suggesting a causative role for MAGP1 in the increased adiposity and predisposition to diabetes. By 5 weeks of age, Mfap2(-/-) mice were maladaptive to cold challenge, uncoupling protein-1 expression was attenuated in the brown adipose tissue, and there was reduced browning of the subcutaneous white adipose tissue. Levels of transforming growth factor-β (TGF-β) activity were elevated in Mfap2(-/-) adipose tissue, and the treatment of Mfap2(-/-) mice with a TGF-β-neutralizing antibody improved their body temperature and prevented the increased adiposity phenotype. Together, these findings indicate that the regulation of TGF-β by MAGP1 is protective against the effects of metabolic stress, and its absence predisposes individuals to metabolic dysfunction.

© 2014 by the American Diabetes Association.

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