Abstract
BackgroundBerberine (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.MethodsThirty-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.ResultsCompared 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).ConclusionsThe 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.
Highlights
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]
Changes of body weight and plasma lipid levels induced by Sim and BBR Rats fed with high fat diet-fed (HFD) tended to developing obesity, shown by increased body weight compared with controls, while either Sim or BBR could decrease the body weight of rats fed with HFD (P < 0.05 respectively)
Sim significantly decreased serum TC and LDL-C (P < 0.05). Both Sim and BBR could increase the serum levels of high density lipoprotein cholesterol (HDL-C), while BBR was more prominent in decreasing serum TG concentration and increasing HDL-C concentration compared with Sim group (P < 0.01 respectively)
Summary
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]. The function of PCSK9, as a secreted serine protease, is degradation of hepatic LDLR, which is directly correlates with its tight association with plasma cholesterol levels and provides a new therapeutic target to combat hypercholesterolemia and CAD [5,6,7,8]. PCSK9 has been identified as a target gene of SREBPs [9,10,11]. 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
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