Enhanced circulating PCSK9 concentration by berberine through SREBP-2 pathway in high fat diet-fed rats
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RESEARCH
Open Access
Enhanced circulating PCSK9 concentration by berberine through SREBP-2 pathway in high fat diet-fed rats Yan-Jun Jia, Rui-Xa Xu, Jing Sun, Yue Tang* and Jian-Jun Li*
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. Keywords: Berberine, Simvastatin, Proprotein convertase subtilisin/kexin type 9, Low density lipoprotein receptor, High fat diet-fed rats
Introduction It has been well established that high total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) are among the most important predictors of future coronary artery disease (CAD) and cardiovascular events [1]. In contrast, reduction in the circulating levels of TC and LDL-C has been demonstrated to significantly reduce the risk for CAD [2]. Therefore, the effective control of dyslipidemia and better understanding of lipid metabolism have been considered as a powerful strategy for the prevention and treatment of CAD [3]. * Correspondence: Tangyue1226@vip. sina.com; [email protected] 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
Recent studies of human genetics and genome-wide screens have identified proprotein convertase subtilisin/ kexin type 9 (PCSK9) as the third gene associated with autosomal dominant familial hypercholesterol
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