title: Induction of heme oxygenase-1 with hemin reduces obesity-induced adipose tissue inflammation via adipose macrophage phenotype switching.
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-κB) 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 PPARγ 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 PPARγ and STAT6 pathway. HO-1 inducers such as hemin may be useful for preventing obesity-induced adipose inflammation.
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Thai Hien
authors.identifier: 0000-0002-6674-012X
authors.initials: TH
authors.lastname: Tu
authors.affiliation: Department of Biological Science, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.affiliation: Department of Biological Science, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Hye-Seon
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Biological Science, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Hun Taeg
authors.identifier: 0000-0003-4802-7467
authors.initials: HT
authors.lastname: Chung
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Rina
authors.identifier: 0000-0002-1965-3891
authors.initials: R
authors.lastname: Yu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D006427:Hemin; D051547:Heme Oxygenase-1