title: Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Chu-Sook
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Yoonhee
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Suck-Young
authors.initials: SY
authors.lastname: Choe
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Sun-Myung
authors.initials: SM
authors.lastname: Hong
authors.affiliation: Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chosun University, Gwangju, 501-759 South Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Yoo
authors.affiliation: Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Hye-Seon
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Hun Taeg
authors.initials: HT
authors.lastname: Chung
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, 680-749 South Korea.
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
keywords: Fatty liver disease; Hepatosteatosis; Mitochondrial oxidative metabolism; Obesity