Reyhan Nergiz-Unal1, Elif Ulug2, Betul Kisioglu2, Funda Tamer2, Mahmut Bodur3, Hacer Yalcimin2, Armagan Aytug Yuruk2. 1. Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey. Electronic address: rnergiz@hacettepe.edu.tr. 2. Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey. 3. Department of Nutrition and Dietetics, Faculty of Health Sciences, Ankara University, Ankara, Turkey.
Abstract
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.
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.
Authors: Xiaoqing Luo; Enze Zheng; Li Wei; Han Zeng; Hong Qin; Xiaoyu Zhang; Meng Liao; Lin Chen; Lei Zhao; Xiong Z Ruan; Ping Yang; Yaxi Chen Journal: Cell Death Dis Date: 2021-03-26 Impact factor: 8.469