Induction of Heme Oxygenase-1 with Hemin Reduces Obesity-Induced Adipose Tissue Inflammation via Adipose Macrophage Phenotype Switching. (11th November 2014)

• Record Type: Journal Article
• Authors: Tu, Thai Hien; Joe, Yeonsoo; Choi, Hye-Seon; Chung, Hun Taeg; Yu, Rina
• Other Names: Valacchi Giuseppe Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2014(2014)
• Publication Date: 2014-11-11
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2014/290708
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Adipose macrophages with the anti-inflammatory M2 phenotype protect against obesity-induced inflammation and insulin resistance. Heme oxygenase-1 (HO-1), which elicits antioxidant and anti-inflammatory activity, modulates macrophage phenotypes and thus is implicated in various inflammatory diseases. Here, we demonstrate that the HO-1 inducer, hemin, protects against obesity-induced adipose inflammation by inducing macrophages to switch to the M2 phenotype. HO-1 induction by hemin reduced the production of proinflammatory cytokines (TNF- α and IL-6) from cocultured adipocytes and macrophages by inhibiting the activation of inflammatory signaling molecules (JNK and NF- κ B) in both cell types. Hemin enhanced transcript levels of M2 macrophage marker genes (IL-4, Mrc1, and Clec10a) in the cocultures, while reducing transcripts of M1 macrophage markers (CD274 and TNF- α ). The protective effects of hemin on adipose inflammation and macrophage phenotype switching were confirmed in mice fed a high-fat diet, and these were associated with PPAR γ upregulation and STAT6 activation. These findings suggest that induction of HO-1 with hemin protects against obesity-induced adipose inflammation through M2 macrophage phenotype switching, which is induced by the PPAR γ and STAT6 pathway. HO-1 inducers such as hemin may be useful for preventing obesity-induced adipose inflammation.