The extracellular matrix protein MAGP1 supports thermogenesis and protects against obesity and diabetes through regulation of TGFβ

  1. Robert P. Mecham1
  1. 1Department of Cell Biology & Physiology,
  2. 2Department of Medicine – Center for Human Nutrition,
  3. 3Department of Medicine - Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine St. Louis, MO, USA 6311
  1. *Corresponding author: Clarissa S. Craft, E-mail: clarissa.craft{at}wustl.edu

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, UCP-1 expression was attenuated in the brown adipose tissue and there was reduced browning of the subcutaneous white adipose tissue. TGFβ activity was elevated in Mfap2-/- adipose tissue and treatment of Mfap2-/- mice with a TGFβ neutralizing antibody improved their body temperature and prevented the increased adiposity phenotype. Together, these findings indicate that MAGP1’s regulation of TGFβ is protective against the effects of metabolic stress, and its absence predisposes to metabolic dysfunction.

  • Received October 17, 2013.
  • Accepted January 17, 2014.

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