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

Authors: Craft, Clarissa S  Pietka, Terri A  Schappe, Timothy  Coleman, Trey  Combs, Michelle D  Klein, Samuel  Abumrad, Nada A  Mecham, Robert P 
Citation: Craft CS, etal., Diabetes. 2014 Jun;63(6):1920-32. doi: 10.2337/db13-1604. Epub 2014 Jan 23.
Pubmed: (View Article at PubMed) PMID:24458361
DOI: Full-text: DOI:10.2337/db13-1604

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-ß (TGF-ß) activity were elevated in Mfap2(-/-) adipose tissue, and the treatment of Mfap2(-/-) mice with a TGF-ß-neutralizing antibody improved their body temperature and prevented the increased adiposity phenotype. Together, these findings indicate that the regulation of TGF-ß by MAGP1 is protective against the effects of metabolic stress, and its absence predisposes individuals to metabolic dysfunction.

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RGD Object Information
RGD ID: 13673807
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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