Alginate oligosaccharide enhances LDL uptake via regulation of LDLR and PCSK9 expression

The Journal of Nutritional Biochemistry
Ji Hye YangSung Hwan Ki

Abstract

The hepatic low-density lipoprotein (LDL) receptor (LDLR) plays a crucial role in lipoprotein metabolism by lowering the plasma LDL-cholesterol concentration, which reduces the risk for cardiovascular diseases. Although alginate oligosaccharide (AOS), prepared from degradation, has several pharmacological effects, it is not known whether AOS affects lipoprotein metabolism. This study was conducted to investigate whether AOS up-regulated LDLR expression and LDL uptake in vitro and in vivo, and the underlying molecular mechanism. We found that AOS increased LDLR expression and intracellular uptake of LDL by hepatocytes in a dose- and time-dependent manner. It is well established that sterol-responsive element binding protein-2 (SREBP-2) is an essential transcription factor for LDLR gene expression. AOS enhanced SREBP-2 nuclear translocation and mRNA levels. The specific role of SREBP-2 activation in AOS-induced LDLR expression was verified using an LDLR promoter construct with a sterol response element deletion. The activation of SREBP-2 by AOS is mediated by phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3β pathways. Furthermore, we found that expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), a cru...Continue Reading

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Citations

Nov 19, 2015·Molecular Nutrition & Food Research·Johann GuillemotNabil G Seidah
Mar 4, 2020·Marine Drugs·Maochen XingShuliang Song
Dec 19, 2020·Comprehensive Reviews in Food Science and Food Safety·Jun LiuZhengqiang Jiang
Jun 14, 2021·Carbohydrate Polymers·Ushasree Mrudulakumari VasudevanEun Yeol Lee
Jul 14, 2021·Critical Reviews in Food Science and Nutrition·Chunhua ZhangChunpeng Wan

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