Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids
Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids
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DOI：
10.1016/j.amjcard.2005.12.024
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发表时间：
2006-08-21
影响因子：
2.8
通讯作者：
Davidson, Michael H.
中科院分区：
文献类型：
--
作者：
Davidson, Michael H.
解释海洋ω-3脂肪酸对人体的降血脂作用的机制尚未阐明。可以在基因转录水平上开发工作模型，其涉及>= 4个代谢核受体。这些包括肝X受体、肝细胞核因子-4 α（HNF-4 α）、法尼醇X受体和过氧化物酶体增殖物激活受体（PPARs）。这些受体中的每一种都受到固醇受体元件结合蛋白-1c（SREBP-1c）的调节，该蛋白是控制脂肪生成的主要遗传开关。Omega-3脂肪酸通过降低SREBP-1c水平协同抑制肝脏脂肪生成、通过激活PPAR上调肝脏和骨骼肌中的脂肪氧化以及通过下调HNF-4 α增强葡萄糖向糖原的流动而引起低血糖效应。最终结果是代谢燃料从甘油三酯储存向氧化的重新分配，从而减少了极低密度脂蛋白（VLDL）合成的底物。通过同时下调编码刺激脂质合成的蛋白质的基因和上调编码刺激脂肪酸氧化的蛋白质的基因，在碳对碳的基础上，ω-3脂肪酸是比ω-6脂肪酸更有效的降血脂剂。此外，ω-3脂肪酸的过氧化可通过刺激载脂蛋白B降解减少VLDL分泌。Omega-3脂肪酸可能通过减少VLDL分泌和直接刺激脂蛋白脂肪酶活性来增强餐后乳糜微粒清除。这些综合作用支持使用ω-3脂肪酸作为治疗高胆固醇血症的有价值的临床工具。(c)2006年爱思唯尔公司All rights reserved.
A mechanism to explain the hypotriglyceridemic effects of marine omega-3 fatty acids in humans has, not been clarified. A working model can be developed at the gene transcriptional level, which involves >= 4 metabolic nuclear receptors. These include liver X receptor, hepatocyte nuclear factor-4 alpha (HNF-4 alpha), farnesol X receptor, and peroxisome proliferator-activated receptors (PPARs). Each of these receptors is regulated by sterol receptor element binding protein-1c (SREBP-1c), the main genetic switch controlling lipogenesis. Omega-3 fatty acids elicit hypotriglyceridemic effects by coordinately suppressing hepatic lipogenesis through reducing levels of SREBP-1c, upregulating fatty oxidation in the liver and skeletal muscle through PPAR activation, and enhancing flux of glucose to glycogen through downregulation of HNF-4 alpha. The net result is the repartitioning of metabolic fuel from triglyceride storage toward oxidation, thereby reducing the substrate available for very-low-density lipoprotein (VLDL) synthesis. By simultaneously downregulating genes encoding proteins that stimulate lipid synthesis and upregulating genes encoding proteins that stimulate fatty acid oxidation, omega-3 fatty acids are more potent hypotriglyceridemic agents than are omega-6 fatty acids, on a carbon-for-carbon basis. Additionally, peroxidation, of omega-3 fatty acids may reduce VLDL secretion through stimulating apolipoprotein B degradation. Omega-3 fatty acids may act by enhancing postprandial chylomicron clearance through reduced VLDL secretion and by directly stimulating lipoprotein lipase activity. These combined effects support the use of omega-3 fatty acids as a valuable clinical tool for the treatment of hypertriglyceridemia. (c) 2006 Elsevier Inc. All rights reserved.