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Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching
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 an...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Nutrition Society and the Korean Society of Community Nutrition
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126412/ https://www.ncbi.nlm.nih.gov/pubmed/27909560 http://dx.doi.org/10.4162/nrp.2016.10.6.623 |
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author | Kim, Chu-Sook Choi, Hye-Seon Joe, Yeonsoo Chung, Hun Taeg Yu, Rina |
author_facet | Kim, Chu-Sook Choi, Hye-Seon Joe, Yeonsoo Chung, Hun Taeg Yu, Rina |
author_sort | Kim, Chu-Sook |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5126412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Korean Nutrition Society and the Korean Society of Community Nutrition |
record_format | MEDLINE/PubMed |
spelling | pubmed-51264122016-12-02 Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching Kim, Chu-Sook Choi, Hye-Seon Joe, Yeonsoo Chung, Hun Taeg Yu, Rina Nutr Res Pract Short Communication 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. The Korean Nutrition Society and the Korean Society of Community Nutrition 2016-12 2016-09-09 /pmc/articles/PMC5126412/ /pubmed/27909560 http://dx.doi.org/10.4162/nrp.2016.10.6.623 Text en ©2016 The Korean Nutrition Society and the Korean Society of Community Nutrition http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Communication Kim, Chu-Sook Choi, Hye-Seon Joe, Yeonsoo Chung, Hun Taeg Yu, Rina Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching |
title | Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching |
title_full | Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching |
title_fullStr | Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching |
title_full_unstemmed | Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching |
title_short | Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching |
title_sort | induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126412/ https://www.ncbi.nlm.nih.gov/pubmed/27909560 http://dx.doi.org/10.4162/nrp.2016.10.6.623 |
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