title: Study on possible mechanism of orotic acid-induced fatty liver in rats.
abstract: OBJECTIVE
  The aim of this study was to investigate the possible mechanism of orotic acid-induced fatty liver in rats.
  
  
  METHODS
  Rats were randomly divided into two groups and fed an AIN-93 diet with 1% orotic acid or without orotic acid for 10 d. Hepatic lipid concentrations, such as triacylglycerol, total cholesterol, and phospholipids, were examined. To clarify the mechanism of orotic acid-induced fatty liver, hepatic enzyme activities and mRNA levels of key enzymes related in lipid metabolism and hepatic gene expression of transcription factors were determined.
  
  
  RESULTS
  Orotic acid administration significantly increased hepatic triacylglycerol concentration. The activity and mRNA level of fatty acid synthase were obviously upregulated by orotic acid treatment, whereas the activities and mRNA concentrations of carnitine palmitoyl transferase and microsomal triacylglycerol transfer protein were significantly depressed. Furthermore, orotic acid stimulated the mRNA expression of sterol regulatory element binding protein-1c but did not alter the mRNA concentration of peroxisome proliferator-activated receptor-α in the liver.
  
  
  CONCLUSIONS
  The stimulation of triacylglycerol synthesis induced by orotic acid is mainly caused by enhancement of sterol regulatory element binding protein-1c and its target gene involved in fatty acid biosynthesis. In contrast, the inhibition of fatty acid β-oxidation and very-low-density lipoprotein secretion were related to the observed lipid accumulation.
authors.affiliation: College of Food Science and Engineering, Ocean University of China, Qingdao, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Wang
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Hu
authors.forename: Yong
authors.initials: Y
authors.lastname: Xue
authors.forename: Zhao-Jie
authors.initials: ZJ
authors.lastname: Li
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Yanagita
authors.forename: Chang-Hu
authors.initials: CH
authors.lastname: Xue
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood / Q000378:metabolism; D004032:Diet; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009963:Orotic Acid / Q000633:toxicity*; D010743:Phospholipids / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D015243:Cholesterol, VLDL; D010743:Phospholipids; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D009963:Orotic Acid; D002784:Cholesterol; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases