title: Osthole improves glucose and lipid metabolism via modulation of PPARα/γ-mediated target gene expression in liver, adipose tissue, and skeletal muscle in fatty liver rats.
abstract: BACKGROUND
  Osthole may be a dual agonist of peroxisome proliferator-activated receptors (PPAR) α/γ and ameliorate the insulin resistance (IR), but its mechanisms are not yet understood completely.
  
  
  OBJECTIVE
  We investigated the effects of osthole on PPARα/γ-mediated target genes involved in glucose and lipid metabolism in liver, adipose tissue, and skeletal muscle in fatty liver and IR rats.
  
  
  METHODS
  The rat model was established by orally feeding high-fat and high-sucrose emulsion for 9 weeks. The experimental rats were treated with osthole 5-10 mg/kg by gavage after feeding the emulsion for 6 weeks, and were sacrificed 4 weeks after administration.
  
  
  RESULTS
  After treatment with osthole 5-10 mg/kg for 4 weeks, the lipid levels in serum and liver were decreased by 37.9-67.2% and 31.4-38.5% for triglyceride, 33.1-47.5% and 28.5-31.2% for free fatty acid, respectively, the fasting blood glucose, fasting serum insulin, and homeostasis model assessment of IR were also decreased by 17.2-22.7%, 25.9-26.7%, and 37.5-42.8%, respectively. Osthole treatment might simultaneously decrease the sterol regulatory element binding protein-1c, diacylglycerol acyltransferase, and fatty acid synthase mRNA expressions in liver and adipose tissue, and increase the carnitine palmitoyltransferase-1A mRNA expression in liver and glucose transporter-4 mRNA expression in skeletal muscle, especially in the osthole 10 mg/kg group (p < 0.01).
  
  
  CONCLUSIONS
  Osthole can improve glucose and lipid metabolism in fatty liver and IR rats, and its mechanisms may be associated with synergic modulation of PPARα/γ-mediated target genes involved in glucose and lipid metabolism in liver, adipose tissue, and skeletal muscle.
authors.affiliation: a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Jiangsu Province , China .|b Department of Pharmacy , Wuxi People's Hospital , Wuxi , Jiangsu Province , China .
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Qi
authors.affiliation: a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Jiangsu Province , China .|c Department of Pharmaceutical Laboratory , School of Pharmacy, Nantong University , Nantong , Jiangsu Province , China , and.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Jiangsu Province , China .|d Department of Pharmacy , the Affiliated Children's Hospital of Soochow University , Suzhou , Jiangsu Province , China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.affiliation: a Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases , College of Pharmaceutical Sciences, Soochow University , Jiangsu Province , China .
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Xie
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018390:Gene Targeting / Q000379:methods; D005947:Glucose / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D003374:Coumarins; D047493:PPAR alpha; D047495:PPAR gamma; D005947:Glucose; C046627:osthol
keywords: Carnitine palmitoyltransferase-1; diacylglycerol acyltransferase; fasting blood glucose; fatty acid synthase; free fatty acid; glucose transporter-4; sterol regulatory element binding protein-1; triglyceride