Oscarsson Jan, Hurt-Camejo Eva
AstraZeneca Gothenburg, Pepparedsleden 1, SE-431 83, Mölndal, Sweden.
Lipids Health Dis. 2017 Aug 10;16(1):149. doi: 10.1186/s12944-017-0541-3.
Epidemiological and genetic studies suggest that elevated triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hypertriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies.
We conducted a review, using systematic methodology, of studies in humans assessing the mechanisms of action of EPA and DHA on apolipoprotein B-containing lipoproteins, including TG-rich lipoproteins and low-density lipoproteins (LDLs). A systematic search of PubMed retrieved 55 articles, of which 30 were used in the review; 35 additional arrticles were also included.
In humans, dietary DHA is retroconverted to EPA, while production of DHA from EPA is not observed. Dietary DHA is preferentially esterified into TGs, while EPA is more evenly esterified into TGs, cholesterol esters and phospholipids. The preferential esterification of DHA into TGs likely explains the higher turnover of DHA than EPA in plasma. The main effects of both EPA and DHA are decreased fasting and postprandial serum TG levels, through reduction of hepatic very-low-density lipoprotein (VLDL)-TG production. The exact mechanism for reduced VLDL production is not clear but does not include retention of lipids in the liver; rather, increased hepatic fatty acid oxidation is likely. The postprandial reduction in TG levels is caused by increased lipoprotein lipase activity and reduced serum VLDL-TG concentrations, resulting in enhanced chylomicron clearance. Overall, no clear differences between the effects of EPA and DHA on TG levels, or on turnover of TG-rich lipoproteins, have been observed. Effects on LDL are complex and may be influenced by genetics, such as APOE genotype.
EPA and DHA diminish fasting circulating TG levels via reduced production of VLDL. The mechanism of reduced VLDL production does not involve hepatic retention of lipids. Lowered postprandial TG levels are also explained by increased chylomicron clearance. Little is known about the specific cellular and biochemical mechanisms underlying the TG-lowering effects of EPA and DHA in humans.
流行病学和遗传学研究表明，循环中富含甘油三酯（TG）的脂蛋白水平升高会增加心血管疾病风险。ω-3脂肪酸（OM3FAs）的处方制剂，主要是二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），可降低血浆TG水平，并被批准用于治疗重度高甘油三酯血症患者。许多临床前研究已经探究了OM3FAs降低TG的作用机制，但临床研究对此了解较少。
我们采用系统方法对评估EPA和DHA对含载脂蛋白B的脂蛋白（包括富含TG的脂蛋白和低密度脂蛋白（LDL））作用机制的人体研究进行了综述。对PubMed进行系统检索后获得55篇文章，其中30篇用于本综述；另外还纳入了35篇文章。
在人体中，膳食中的DHA可逆向转化为EPA，但未观察到由EPA生成DHA的情况。膳食中的DHA优先酯化到TG中，而EPA则更均匀地酯化到TG、胆固醇酯和磷脂中。DHA优先酯化到TG中可能解释了其在血浆中的周转率高于EPA。EPA和DHA的主要作用都是通过减少肝脏极低密度脂蛋白（VLDL）-TG的生成，降低空腹和餐后血清TG水平。VLDL生成减少的确切机制尚不清楚，但不包括脂质在肝脏中的潴留；相反，肝脏脂肪酸氧化增加可能是原因。餐后TG水平的降低是由于脂蛋白脂肪酶活性增加和血清VLDL-TG浓度降低，导致乳糜微粒清除增强。总体而言，未观察到EPA和DHA在降低TG水平或富含TG脂蛋白周转率方面的明显差异。对LDL的影响较为复杂，可能受遗传学因素影响，如APOE基因型。
EPA和DHA通过减少VLDL生成降低空腹循环TG水平。VLDL生成减少的机制不涉及肝脏脂质潴留。餐后TG水平降低也可归因于乳糜微粒清除增加。关于EPA和DHA在人体中降低TG作用的具体细胞和生化机制知之甚少。
