title: Enhanced circulating PCSK9 concentration by berberine through SREBP-2 pathway in high fat diet-fed rats.
abstract: BACKGROUND
  Berberine (BBR), a natural plant extract, has been shown to improve lipid metabolism. However, its effects on PCSK9, a key factor involving in the lipid metabolism, have not yet been evaluated in vivo. The aim of the present study was to investigate the effect of BBR on PCSK9 expression in high fat diet-fed (HFD) rats.
  
  
  METHODS
  Thirty-two male Sprague Dawley (SD) rats were randomized into the four groups (n = 8): normal diet (Control), HFD, HFD + simvastatin (Sim, 2 mg/kg/d) and HDF + BBR (400 mg/kg/d) for 6 weeks. The following parameters were determined: 1) body weight; 2) serum lipid profile; 3) serum PCSK9 measured by enzyme-linked immuno sorbent assay (ELISA) ; 4) hepatic expressions of low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1 (HNF1) were examined by real time quantitative polymerase chain reaction (RT-PCR) and western blotting analysis.
  
  
  RESULTS
  Compared with HFD rats, Sim and BBR significantly reduced body weight gain and improved lipid profile (P < 0.05 respectively). In addition, either of drug treatment for 6 weeks could increase serum concentration of PCSK9 in HFD rats (P < 0.05). This enhanced PCSK9 expression was demonstrated to be associated with the up-regulation of hepatic expression of LDLR and SREBP-2 and the down-regulation of hepatic expression of HNF1 (P < 0.05 respectively).
  
  
  CONCLUSIONS
  The data provided the first line of the evidence that BBR, similar to the Sim, could increase the expression of PCSK9 levels in HFD rats through SREBP-2 activation, suggesting that impacts of BBR on lipid profile may also be linked to SREBP-2 pathway.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Jia
authors.forename: Rui-Xa
authors.initials: RX
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Tangyue1226@vip.sina.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D001599:Berberine / Q000494:pharmacology*; D017931:DNA Primers; D059305:Diet, High-Fat; D008297:Male; D000071449:Proprotein Convertase 9; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000097:blood*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D051782:Sterol Regulatory Element Binding Protein 2; D001599:Berberine; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D012697:Serine Endopeptidases
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