Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching.
10.4162/nrp.2016.10.6.623
- Author:
Chu Sook KIM
1
;
Hye Seon CHOI
;
Yeonsoo JOE
;
Hun Taeg CHUNG
;
Rina YU
Author Information
1. Department of Food Science and Nutrition, University of Ulsan, 93 Daehak-ro, Nam-ku, Ulsan 44610, Korea. rinayu@ulsan.ac.kr
- Publication Type:Brief Communication
- Keywords:
Obesity;
quercetin;
inflammation;
macrophage
- MeSH:
Animals;
Blotting, Western;
Coculture Techniques;
Cytokines;
Diet;
Diet, High-Fat;
Down-Regulation;
Enzyme-Linked Immunosorbent Assay;
Fatty Liver;
Heme Oxygenase-1*;
Heme*;
Hepatocytes;
Humans;
Inflammation*;
Insulin Resistance;
Liver;
Macrophages*;
Male;
Mice;
NF-E2-Related Factor 2;
Obesity;
Phenotype*;
Quercetin*;
Up-Regulation
- From:Nutrition Research and Practice
2016;10(6):623-628
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines (TNFα, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes (TNFα, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.
