Hepatic cholesterol synthesis and lipoprotein levels impaired by dietary fructose and saturated fatty acids in mice: Insight on PCSK9 and CD36
Hepatic cholesterol synthesis and lipoprotein levels impaired by dietary fructose and saturated fatty acids in mice: Insight on PCSK9 and CD36
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DOI：
10.1016/j.nut.2020.110954
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发表时间：
2020-11-01
期刊：
影响因子：
4.4
通讯作者：
Yuruk, Armagan Aytug
中科院分区：
文献类型：
--
作者：
Nergiz-Unal, Reyhan;Ulug, Elif;Yuruk, Armagan Aytug
目的：本研究的目的是研究高饱和脂肪酸（SFAs）或果糖摄入对胆固醇和脂蛋白的不确定影响，并深入了解前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）和分化簇36（CD 36）诱导的机制。40只雄性C57 BL/6小鼠（8周龄）随机分为4组，分别饲喂标准饲料和3种高脂肪酸等热量饲料（SFA组），单不饱和脂肪酸随后，处死小鼠，收集血液、肝脏和心脏用于进一步分析。因此，果糖或SFA摄入导致血浆和肝脏总胆固醇（TC）水平、血浆低密度脂蛋白胆固醇（LDL-C）、非高密度脂蛋白胆固醇（HDL-C）、血浆载脂蛋白（Apo）-B水平、TC/HDL-C、LDL-C/HDL-C比值、HDL-C和Apo-A1水平降低（P < 0.05）。高SFAs和果糖摄入使肝脏3-羟基-3-甲基戊二酰辅酶A还原酶和乙酰辅酶A乙酰转移酶1水平以及血浆CD 36水平升高（P < 0.05），而血浆PCSK 9水平无显著变化。果糖和SFA摄入量增加了心脏中的PCSK 9和CD 36水平，沿着增加了肝脏中的CD 36水平（P < 0.05）。此外，发现血浆LDL-C与肝脏PCSK 9正相关（r = 0.85，P = 0.02），CD36（r = 0.70，P = 0.02）。结论：高摄入量的膳食脂肪酸和果糖可能会诱导胆固醇合成和血脂水平的失调，通过建议的营养素-肝和肝外组织中涉及胆固醇稳态的敏感生物标志物PCSK 9和CD 36。(C)2020爱思唯尔公司All rights reserved.
Objectives: The aim of this study was to investigate the uncertain effects of high saturated fatty acids (SFAs) or fructose intake on cholesterol and lipoproteins with an insight of proprotein convertase subtilisin/kexin type 9 (PCSK9)- and cluster of differentiation 36 (CD36)-induced mechanisms.Methods: Forty male C57 BL/6 mice (8 wks of age) were divided into four groups and fed ad libitum with standard chow or three isocaloric diets containing high SFAs (SFA group), monounsaturated fatty acids (MUFA group, vehicle), or fructose for 15 wks. Subsequently, mice were sacrificed and blood, liver, and heart were collected for further analysis.Results: Consequently, fructose or SFA intake resulted in higher plasma and liver total cholesterol (TC) levels, plasma low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo)-B levels, TC/HDL-C, and LDL-C/HDL-C ratios, and lower plasma levels of HDL-C and Apo-A1 (P < 0.05). Levels of 3-hydroxy-3-methylglutaryl-CoA reductase and acetyl-CoA acetyltransferase 1 enzymes in liver and CD36 levels in plasma were elevated by high SFAs and fructose intake (P < 0.05), whereas plasma PCSK9 levels were not significantly changed. Fructose and SFA intake increased PCSK9 and CD36 levels in the heart, along with increased CD36 levels in the liver (P < 0.05). Furthermore, plasma LDL-C was found to be positively correlated with liver PCSK9 (r = 0.85, P = 0.02), and CD36 (r = 0.70, P = 0.02) in the SFA and fructose groups.Conclusion: High intakes of dietary SFAs and fructose might induce dysregulations in the cholesterol synthesis and blood lipoprotein levels via proposed nutrient-sensitive biomarkers PCSK9 and CD36 in liver and extrahepatic tissues involved in cholesterol homeostasis. (C) 2020 Elsevier Inc. All rights reserved.