| Autor: |
Craft, Clarissa S., Pietka, Terri A., Schappe, Timothy, Coleman, Trey, Combs, Michelle D., Klein, Samuel, Abumrad, Nada A., Mecham, Robert P. |
| Zdroj: |
Diabetes; Jun2014, Vol. 63 Issue 6, p1920-1932, 13p, 1 Chart, 7 Graphs |
| Abstrakt: |
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-b (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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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