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タイトル: | Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1 |
著者: | Kim, Chu Sook Kwon, Yoonhee Choe, Suck Young Hong, Sun Myung Yoo, Hoon Goto, Tsuyoshi https://orcid.org/0000-0003-1283-147X (unconfirmed) Kawada, Teruo Choi, Hye Seon Joe, Yeonsoo Chung, Hun Taeg Yu, Rina |
著者名の別形: | 後藤, 剛 河田, 照雄 |
キーワード: | Obesity Hepatosteatosis Fatty liver disease Mitochondrial oxidative metabolism |
発行日: | 6-Oct-2015 |
出版者: | BioMed Central Ltd. |
誌名: | Nutrition and Metabolism |
巻: | 12 |
論文番号: | 33 |
抄録: | Background: Obesity-induced hepatic lipid accumulation causes lipotoxicity, mitochondrial dysfunction, oxidative stress, and insulin resistance, and is implicated in non-alcoholic hepatic pathologies such as steatohepatitis and fibrosis. Heme oxygenase-1 (HO-1), an important antioxidant enzyme catalyzing the rate-limiting step in heme degradation, protects against oxidative stress, inflammation, and metabolic dysregulation. Here, we demonstrate that the phytochemical, quercetin, a natural polyphenol flavonoid, protects against hepatic steatosis in obese mice fed a high-fat diet, and that it does so by inducing HO-1 and stimulating increased hepatic mitochondrial oxidative metabolism. Methods: Male C57BL/6 mice were fed a regular diet (RD), a high-fat diet (HFD), and an HFD supplemented with quercetin for 9 weeks. Levels of mitochondrial biogenesis and oxidative metabolic transcripts/proteins were measured by real-time PCR and/or Western blotting. HO-1 transcripts/proteins were measured real-time PCR and/or Western blotting. Results: Quercetin upregulated genes involved in mitochondrial biogenesis and oxidative metabolism in lipid-laden hepatocytes and the livers of HFD-fed obese mice, and this was accompanied by increased levels of the transcription factor, nuclear erythroid 2-related factor 2 (Nrf-2), and HO-1 protein. The HO-1 inducer hemin and the HO-1 byproduct carbon monoxide (CO) also enhanced hepatic oxidative metabolism in HFD-fed obese mice. Moreover, the metabolic changes and the lipid-lowering effects of quercetin were completely blocked by the HO-1 inhibitor ZnPP and by deficiency of Nrf-2. Conclusion: These findings suggest that quercetin stimulates hepatic mitochondrial oxidative metabolism by inducing HO-1 via the Nrf-2 pathway. Quercetin may be useful in protecting against obesity-induced hepatosteatosis. |
著作権等: | © 2015 Kim et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
URI: | http://hdl.handle.net/2433/212478 |
DOI(出版社版): | 10.1186/s12986-015-0030-5 |
PubMed ID: | 26445592 |
出現コレクション: | 学術雑誌掲載論文等 |
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