Wang Yu, Zhao Jiajia, Li Qiang, Liu Jinxin, Sun Yujie, Zhang Kuiliang, Fan Mingcong, Qian Haifeng, Li Yan, Wang Li
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.
College of Cooking Science and Technology, Jiangsu College of Tourism, Yangzhou, 225000, China.
Nutr Metab (Lond). 2022 Apr 15;19(1):30. doi: 10.1186/s12986-022-00662-8.
Hypercholesterolemia is closely associated with an increased risk of cardiovascular diseases. L-Arabinose exhibited hypocholesterolemia properties, but underlying mechanisms have not been sufficiently investigated. This study aimed to elucidate the mechanisms of L-arabinose on hypocholesterolemia involving the enterohepatic circulation of bile acids.
Thirty six-week-old male mice were randomly divided into three groups: the control group and the high-fat-high-sucrose diet (HFHSD)-fed group were gavaged with distilled water, and the L-arabinose-treated group were fed HFHSD and received 400 mg/kg/day L-arabinose for 12 weeks. Serum and liver biochemical parameters, serum and fecal bile acid, cholesterol and bile acid metabolism-related gene and protein expressions in the liver and small intestine were analyzed.
L-Arabinose supplementation significantly reduced body weight gain, lowered circulating low-density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C) levels, and efficiently alleviated hepatic inflammation and lipid accumulations in HFHSD-fed mice. L-Arabinose inhibited cholesterol synthesis via downregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Additionally, L-arabinose might facilitate reverse cholesterol transport, evidenced by the increased mRNA expressions of low-density lipoprotein receptor (LDL-R) and scavenger receptor class B type 1 (SR-B1). Furthermore, L-arabinose modulated ileal reabsorption of bile acids mainly through downregulation of ileal bile acid-binding protein (I-BABP) and apical sodium-dependent bile acid transporter (ASBT), resulting in the promotion of hepatic synthesis of bile acids via upregulation of cholesterol-7α-hydroxylase (CYP7A1).
L-Arabinose supplementation exhibits hypocholesterolemic effects in HFHSD-fed mice primarily due to regulation of bile acid metabolism-related pathways.
高胆固醇血症与心血管疾病风险增加密切相关。L-阿拉伯糖具有降胆固醇特性，但其潜在机制尚未得到充分研究。本研究旨在阐明L-阿拉伯糖降胆固醇作用涉及胆汁酸肝肠循环的机制。
将36只六周龄雄性小鼠随机分为三组：对照组和高脂高糖饮食（HFHSD）喂养组灌胃蒸馏水，L-阿拉伯糖处理组给予HFHSD并接受400mg/kg/天的L-阿拉伯糖，持续12周。分析血清和肝脏生化参数、血清和粪便胆汁酸、胆固醇以及肝脏和小肠中胆汁酸代谢相关基因和蛋白表达。
补充L-阿拉伯糖显著降低体重增加，降低循环低密度脂蛋白胆固醇（LDL-C）水平，同时提高高密度脂蛋白胆固醇（HDL-C）水平，并有效减轻HFHSD喂养小鼠的肝脏炎症和脂质蓄积。L-阿拉伯糖通过下调3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）抑制胆固醇合成。此外，L-阿拉伯糖可能促进胆固醇逆向转运，低密度脂蛋白受体（LDL-R）和B1型清道夫受体（SR-B1）的mRNA表达增加证明了这一点。此外，L-阿拉伯糖主要通过下调回肠胆汁酸结合蛋白（I-BABP）和顶端钠依赖性胆汁酸转运体（ASBT）调节胆汁酸的回肠重吸收，通过上调胆固醇7α-羟化酶（CYP7A1）促进肝脏胆汁酸合成。
补充L-阿拉伯糖对HFHSD喂养的小鼠具有降胆固醇作用，主要是由于调节了胆汁酸代谢相关途径。
