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: Thai Hien Tu, Yeonsoo Joe, Hye-Seon Choi, Hun Taeg Chung, Rina Yu
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2014 Pg. 290708 ( 2014) ISSN: 1466-1861 [Electronic] United States
• PMID: 25477711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Inflammation Mediators
• Hemin
• Heme Oxygenase-1

Topics

• 3T3-L1 Cells
• Adipocytes (drug effects, metabolism, pathology)
• Adipose Tissue (drug effects, metabolism, pathology)
• Animals
• Cell Line
• Coculture Techniques
• Cytokines (metabolism)
• Enzyme Induction (drug effects)
• Heme Oxygenase-1 (biosynthesis)
• Hemin (pharmacology)
• Inflammation (metabolism, pathology, prevention & control)
• Inflammation Mediators (metabolism)
• Macrophages (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (drug therapy, metabolism, pathology)
• Phenotype
• Signal Transduction (drug effects)