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

Clarissa S. Craft, Terri A. Pietka, Timothy Schappe, Trey Coleman, Michelle D. Combs, Samuel Klein, Nada A. Abumrad, Robert P. Mecham

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish
Pages (from-to)1920-1932
Number of pages13
JournalDiabetes
Volume63
Issue number6
DOIs
StatePublished - Jun 2014

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