title: Osthol attenuates hepatic steatosis via decreased triglyceride synthesis not by insulin resistance.
abstract: OBJECTIVE
  To evaluate the effects of osthol on intrahepatic fat synthesis, β-oxidation, inflammation, and insulin resistance by multifaceted analysis.
  
  
  METHODS
  Sprague-Dawley rats (n = 30) were randomly divided into control, non-alcoholic fatty liver disease (NAFLD), and osthol groups. NAFLD and osthol groups were fed with a high-fat diet for 14 wk. After 8 wk of the high-fat diet, the osthol group also received osthol 20 mg/kg orally 5 times/wk. To assess the insulin resistance, oral glucose tolerance was performed at the end of 14 wk. Immunohistochemical (4-HNE, F4/80) and hematoxylin and eosin (HE) staining were performed on liver tissue extracts after animal sacrifice at 14 wk. SREBP1c, FAS, SCD-1, PPAR-α, CROT, MCP-1, IRS-1, and IRS-2 mRNA expressions were assessed with reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  HE staining revealed that, compared with the NAFLD group, the osthol group showed significantly decreased intrahepatic fat content (39.4% vs 21.0%; P = 0.021). SREBP1c expression in the NAFLD group increased compared to controls (P = 0.0001), while osthol treatment decreased SREBP1c expression compared with the NAFLD group (P = 0.0059). In the osthol group, intrahepatic FAS and SCD-1, which act downstream of SREBP1c, decreased significantly compared with the NAFLD group. Moreover, PPAR-α expression in the osthol group was also significantly higher than in the NAFLD group (P = 0.0147).
  
  
  CONCLUSIONS
  Osthol treatment attenuated liver steatosis by decreasing de novo liver triglyceride synthesis and had nominal effects on insulin resistance and liver inflammation.
authors.affiliation: Ho Hyun Nam, Dae Won Jun, Jai Sun Lee, Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul 133-791, South Korea.
authors.forename: Ho Hyun
authors.initials: HH
authors.lastname: Nam
authors.affiliation: Ho Hyun Nam, Dae Won Jun, Jai Sun Lee, Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul 133-791, South Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Jun
authors.affiliation: Ho Hyun Nam, Dae Won Jun, Jai Sun Lee, Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul 133-791, South Korea.
authors.forename: Hye Joon
authors.initials: HJ
authors.lastname: Jeon
authors.affiliation: Ho Hyun Nam, Dae Won Jun, Jai Sun Lee, Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul 133-791, South Korea.
authors.forename: Jai Sun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Ho Hyun Nam, Dae Won Jun, Jai Sun Lee, Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul 133-791, South Korea.
authors.forename: Waqar Khalid
authors.initials: WK
authors.lastname: Saeed
authors.affiliation: Ho Hyun Nam, Dae Won Jun, Jai Sun Lee, Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul 133-791, South Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D015415:Biomarkers; D003374:Coumarins; D014280:Triglycerides; C046627:osthol
keywords: Non-alcoholic fatty liver disease; Osthol; Sterol regulatory element binding protein