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Mice Fed a High‐Cholesterol Diet Supplemented with Quercetin‐3‐Glucoside Show Attenuated Hyperlipidemia and Hyperinsulinemia Associated with Differential Regulation of PCSK9 and LDLR in their Liver and Pancreas
Author(s) -
Mbikay Majambu,
Mayne Janice,
Sirois Francine,
Fedoryak Olesya,
Raymond Angela,
Noad Jennifer,
Chrétien Michel
Publication year - 2018
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700729
Subject(s) - endocrinology , medicine , ldl receptor , pcsk9 , hyperinsulinemia , hyperlipidemia , cholesterol , apolipoprotein b , kexin , biology , insulin , chemistry , lipoprotein , diabetes mellitus , insulin resistance
Scope Hepatic LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) regulate the clearance of plasma LDL‐cholesterol (LDL‐C): LDLR promotes it, and PCSK9 opposes it. These proteins also express in pancreatic β cells. Using cultured hepatocytes, we previously showed that the plant flavonoid quercetin‐3‐glucoside (Q3G) inhibits PCSK9 secretion, stimulated LDLR expression, and enhanced LDL‐C uptake. Here, we examine whether Q3G supplementation could reverse the hyperlipidemia and hyperinsulinemia of mice fed a high‐cholesterol diet, and how it affects hepatic and pancreatic LDLR and PCSK9 expression. Methods and results For 12 weeks, mice are fed a low‐ (0%) or high‐ (1%) cholesterol diet (LCD or HCD), supplemented or not with Q3G at 0.05 or 0.1% (w/w). Tissue LDLR and PCSK9 is analyzed by immunoblotting, plasma PCSK9 and insulin by ELISA, and plasma cholesterol and glucose by colorimetry. In LCD‐fed mice, Q3G has no effect. In HCD‐fed mice, it attenuates the increase in plasma cholesterol and insulin, accentuates the decrease in plasma PCSK9, and increases hepatic and pancreatic LDLR and PCSK9. In cultured pancreatic β cells, however, it stimulates PCSK9 secretion. Conclusion In mice, dietary Q3G could counter HCD‐induced hyperlipidemia and hyperinsulinemia, in part by oppositely modulating hepatic and pancreatic PCSK9 secretion.