Jiangxi Province Key Laboratory of Edible and Medicinal Resources Exploitation, School of Resource and Environmental and Chemical Engineering, Nanchang University, Nanchang 330031, China.
State Key Laboratory of Food Science and Technology, Jiangxi Province Key Laboratory of Edible and Medicinal Resources Exploitation, School of Food Science and Technology, Nanchang University, Nanchang 330031, China.
J Agric Food Chem. 2021 Apr 21;69(15):4453-4463. doi: 10.1021/acs.jafc.1c00745. Epub 2021 Apr 12.
Hypercholesterolemia is often considered to be a major risk factor for atherosclerosis, and medium-chain fatty acids have been found to reduce the total cholesterol (TC) level and maintain low-density lipoprotein cholesterol (LDL-c) stability. However, we unexpectedly found that the levels of TC and LDL-c were increased in obese rats treated with high-dose lauric triglycerides (LT). The study aimed to investigate the effect and mechanism of LT on cholesterol metabolism in obese rats. Our results showed that LT intervention could reduce cholesterol biosynthesis by downregulating the expression of HMG-CoA reductase in obese rats. LT increased the expression levels of PPARγ1, LXRα, ABCA1, and ABCG8 in the liver. These results indicated that LT could improve the lipid transfer and bile acid efflux. However, LT significantly increased the expression of PCSK 9, resulting in accelerated degradation of LDLR, thus reducing the transport of very LDL (VLDL) and LDL to the liver. Together with the increased expression of NPC1L1 protein, LT impaired the uptake of VLDL/LDL by the liver and increased the reabsorption of sterols, leading to an increase in the levels of TC and LDL-c in obese rats.
高胆固醇血症通常被认为是动脉粥样硬化的一个主要危险因素，而中链脂肪酸已被发现可降低总胆固醇（TC）水平并维持低密度脂蛋白胆固醇（LDL-c）的稳定性。然而，我们意外地发现，给予高剂量月桂酸三酸甘油酯（LT）治疗的肥胖大鼠 TC 和 LDL-c 水平升高。本研究旨在探讨 LT 对肥胖大鼠胆固醇代谢的影响及其机制。我们的结果表明，LT 干预可通过下调肥胖大鼠 HMG-CoA 还原酶的表达来减少胆固醇的生物合成。LT 增加了肝脏中 PPARγ1、LXRα、ABCA1 和 ABCG8 的表达水平。这些结果表明 LT 可改善脂质转运和胆汁酸外排。然而，LT 显著增加了 PCSK9 的表达，导致 LDLR 的降解加速，从而减少了 VLDL 和 LDL 向肝脏的转运。与 NPC1L1 蛋白表达增加相结合，LT 损害了肝脏对 VLDL/LDL 的摄取，并增加了固醇的重吸收，导致肥胖大鼠 TC 和 LDL-c 水平升高。
