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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Diabetes 2014 ; 63 (6): 1920-32 Nephropedia Template TP
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The Extracellular Matrix Protein MAGP1 Supports Thermogenesis and Protects Against Obesity and Diabetes Through Regulation of TGF-? #MMPMID24458361
Craft CS; Pietka TA; Schappe T; Coleman T; Combs MD; Klein S; Abumrad NA; Mecham RP
Diabetes 2014[Jun]; 63 (6): 1920-32 PMID24458361show ga
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-? (TGF-?) activity were elevated in Mfap2?/? adipose tissue, and the treatment of Mfap2?/? mice with a TGF-??neutralizing antibody improved their body temperature and prevented the increased adiposity phenotype. Together, these findings indicate that the regulation of TGF-? by MAGP1 is protective against the effects of metabolic stress, and its absence predisposes individuals to metabolic dysfunction.