| Title | Increased angiogenesis protects against adipose hypoxia and fibrosis in metabolic disease-resistant 11β-hydroxysteroid dehydrogenase type 1 (HSD1)-deficient mice. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Michailidou Z, Turban S, Miller E, Zou X, Schrader J, Ratcliffe PJ, Hadoke PW, Walker BR, Iredale JP, Morton NM, Seckl JR |
| Journal | The Journal of biological chemistry |
| Volume | 287 |
| Issue | 6 |
| Pagination | 4188-97 |
| Date Published | 2012 Feb 3 |
| ISSN | 1083-351X |
| Keywords | 11-beta-Hydroxysteroid Dehydrogenase Type 1, Actins, Adipose Tissue, Angiopoietins, Animals, Anoxia, Fibrosis, Hypoxia-Inducible Factor 1, alpha Subunit, Insulin Resistance, Intercellular Signaling Peptides and Proteins, Male, Mice, Mice, Knockout, Neovascularization, Physiologic, Obesity, PPAR gamma, Signal Transduction, Smad3 Protein, Transforming Growth Factor beta, Vascular Endothelial Growth Factor A, Weight Gain |
| Abstract | 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 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1(-/-)) have "healthier" adipose tissue distribution and resist metabolic disease with diet-induced obesity. Here we show that adipose tissues of 11βHSD1(-/-) mice exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1α) activation of the TGF-β/Smad3/α-smooth muscle actin (α-SMA) signaling pathway, and fibrogenesis despite similar fat accretion with diet-induced obesity. Moreover, augmented 11βHSD1(-/-) adipose tissue angiogenesis is associated with enhanced peroxisome proliferator-activated receptor γ (PPARγ)-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. |
| Alternate Journal | J. Biol. Chem. |
