Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1

Nutrition & Metabolism

Rina Yu²  Hun Taeg Chung³  Yeonsoo Joe³  Hye-Seon Choi³  Teruo Kawada¹  Tsuyoshi Goto¹  Hoon Yoo⁴  Sun-Myung Hong²  Suck-Young Choe²  Yoonhee Kwon²  Chu-Sook Kim² 

[1] Graduate School of Agriculture, Kyoto University, Uji 611-0011, Kyoto, Japan;Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, South Korea;Department of Biological Sciences, University of Ulsan, Ulsan 680-749, South Korea;Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chosun University, Gwangju 501-759, South Korea

关键词: Mitochondrial oxidative metabolism;    Fatty liver disease;    Hepatosteatosis;    Obesity;   

Others  :  1228214
DOI  :  10.1186/s12986-015-0030-5

 received in 2015-07-01, accepted in 2015-09-28,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Kim et al.

【 图 表 】

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