title: Ursolic acid improves lipid and glucose metabolism in high-fat-fed C57BL/6J mice by activating peroxisome proliferator-activated receptor alpha and hepatic autophagy.
abstract: METHODS
  This study investigated metabolic effects of ursolic acid (UA), a peroxisome proliferation-activated receptor (PPAR)-α activator, in vivo.
  
  
  RESULTS
  High-fat diet (HFD)-fed C57BL/6J mice were orally administered UA (50 or 200 mg/kg body weight) for 8 wk. UA reduced liver and adipose tissue mass, adipocyte size, and plasma leptin concentrations, plasma triglyceride and low-density-lipoprotein cholesterol concentrations, while it elevated the high-density-lipoprotein cholesterol and adiponectin concentrations significantly compared with controls. UA induced the expression of PPARα and its responsive genes involved in fatty acid uptake and β-oxidation in the livers, whereas genes involved in lipogenesis, including sterol regulatory element-binding proteins-1c, were downregulated. UA administration improved glucose tolerance and insulin sensitivity significantly compared with the HFD-fed control livers. UA administration also activated hepatic autophagy as assessed by the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II and other key proteins in the autophagy pathway.
  
  
  CONCLUSIONS
  Our findings suggest that UA ameliorates lipid and glucose metabolism in HFD-fed mice primarily by the activation of PPARα and induction of the hepatic autophagy pathway. Thus, intake of UA in the diet or in an isolated form may ameliorate lipid and glucose metabolism.
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences & Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Seyoung
authors.initials: S
authors.lastname: Kim
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Bobae
authors.initials: B
authors.lastname: Kim
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wu
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Hee-jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Nahyun
authors.initials: N
authors.lastname: Kim
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000008:administration & dosage; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014315:Triterpenes / Q000008:administration & dosage*; D000097245:Ursolic Acid
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D002784:Cholesterol; D005227:Fatty Acids; D020738:Leptin; D008869:Microtubule-Associated Proteins; D047493:PPAR alpha; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D014315:Triterpenes; D000097245:Ursolic Acid; C490547:MAP1A protein, mouse; C480860:Map1lc3b protein, mouse; C497388:Srebf1 protein, mouse
keywords: Autophagy; Glucose metabolism; Lipid metabolism; PPARα; Ursolic acid