| First Author | Michailidou Z | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 6 | Pages | 4188-97 |
| PubMed ID | 22158867 | Mgi Jnum | J:181515 |
| Mgi Id | MGI:5311539 | Doi | 10.1074/jbc.M111.259325 |
| Citation | Michailidou Z, et al. (2012) Increased angiogenesis protects against adipose hypoxia and fibrosis in metabolic disease-resistant 11beta-hydroxysteroid dehydrogenase type 1 (HSD1)-deficient mice. J Biol Chem 287(6):4188-97 |
| abstractText | In obesity, rapidly expanding adipose tissue becomes hypoxic, precipitating inflammation, fibrosis, and insulin resistance. Compensatory angiogenesis may prevent these events. Mice lacking the intracellular glucocorticoid-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1(-/-)) have "healthier" adipose tissue distribution and resist metabolic disease with diet-induced obesity. Here we show that adipose tissues of 11betaHSD1(-/-) mice exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1alpha) activation of the TGF-beta/Smad3/alpha-smooth muscle actin (alpha-SMA) signaling pathway, and fibrogenesis despite similar fat accretion with diet-induced obesity. Moreover, augmented 11betaHSD1(-/-) adipose tissue angiogenesis is associated with enhanced peroxisome proliferator-activated receptor gamma (PPARgamma)-inducible expression of the potent angiogenic factors VEGF-A, apelin, and angiopoietin-like protein 4. Improved adipose angiogenesis and reduced fibrosis provide a novel mechanism whereby suppression of intracellular glucocorticoid regeneration promotes safer fat expansion with weight gain. |
