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Increased Angiogenesis Protects against Adipose Hypoxia and Fibrosis in Metabolic Disease-resistant 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD1)-deficient Mice

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http://www.jbc.org/content/287/6/4188
Original languageEnglish
Pages (from-to)4188-4197
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number6
DOIs
Publication statusPublished - 3 Feb 2012

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 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1(-/-)) have "healthier" adipose tissue distribution and resist metabolic disease with diet-induced obesity. Here we show that adipose tissues of 11 beta HSD1(-/-) mice exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1 alpha) 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 11 beta HSD1(-/-) adipose tissue angiogenesis is associated with enhanced peroxisome proliferator-activated receptor gamma (PPAR gamma)-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.

    Research areas

  • Adipose Tissue , Collagen , Extracellular Matrix Proteins , Fibroblast , Hypoxia , Angiogenesis , Fibrosis , Glucocorticoids

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