Ton Mimi N, Chang Chuchun, Carpentier Yvon A, Deckelbaum Richard J
Division of Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
Clin Nutr. 2005 Aug;24(4):492-501. doi: 10.1016/j.clnu.2005.03.001. Epub 2005 Apr 9.
BACKGROUND & AIMS: The triglyceride (TG) fatty acyl composition in lipid emulsions influences their metabolism. Little is known about the effects of long chain omega-3 polyunsaturated fatty acids (PUFA) on lipid emulsion metabolism. We investigated possible differences between omega-3 containing emulsions in their metabolism and tissue-targeting in vivo in a mouse model, and in vitro using lipolysis and cell culture experiments.
Soy oil (LCT), MCT/LCT/omega-3 (5:4:1, wt/wt/wt), and MCT/omega-3 (8:2, wt/wt) emulsions were radiolabeled with nondegradable 1alpha,2alpha (n)-[3H] cholesteryl oleoyl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection. Blood samples obtained over 25 min and extracted organs were used to measure the tissue distribution of lipid emulsion particles. Lipoprotein lipase (LpL)-mediated hydrolysis experiments and cell uptake studies in cultured J774 murine macrophages were also performed.
Blood clearance of 8:2 was 13.4% and 29.8% faster compared to 5:4:1 and LCT, respectively. LCT had greatest liver uptake. LpL-mediated hydrolysis was greatest in 8:2 and lowest in LCT. Overall, cell TG accumulation in the presence of apolipoprotein E was least with 8:2.
Our data shows that 8:2 had the most efficient blood clearance but less hepatic uptake in vivo. In vitro, 8:2 had both highest hydrolysis by LpL and intracellular TG utilization in the presence of apoE. Thus, an 8:2 lipid emulsion undergoes efficient blood clearance and may direct omega-3 PUFA more towards extrahepatic tissues.
脂质乳剂中的甘油三酯(TG)脂肪酸组成会影响其代谢。关于长链ω-3多不饱和脂肪酸(PUFA)对脂质乳剂代谢的影响知之甚少。我们在小鼠模型中研究了含ω-3的乳剂在体内代谢和组织靶向方面的可能差异,并通过体外脂解和细胞培养实验进行了研究。
用不可降解的1α,2α(n)-[3H]胆固醇油酰醚对大豆油(LCT)、中链甘油三酯/长链甘油三酯/ω-3(5:4:1,重量/重量/重量)和中链甘油三酯/ω-3(8:2,重量/重量)乳剂进行放射性标记,以追踪单次注射后C57BL/6J小鼠体内核心颗粒的代谢。在25分钟内采集的血样和提取的器官用于测量脂质乳剂颗粒的组织分布。还进行了脂蛋白脂肪酶(LpL)介导的水解实验以及在培养的J774小鼠巨噬细胞中的细胞摄取研究。
与5:4:1和LCT相比,8:2的血液清除率分别快13.4%和29.8%。LCT在肝脏中的摄取量最大。LpL介导的水解在8:2中最大,在LCT中最低。总体而言,在载脂蛋白E存在的情况下,8:2导致的细胞TG积累最少。
我们的数据表明,8:2具有最有效的血液清除率,但在体内肝脏摄取较少。在体外,8:2在载脂蛋白E存在的情况下,LpL水解率最高且细胞内TG利用率最高。因此,8:2脂质乳剂具有高效的血液清除率,并且可能使ω-3 PUFA更多地导向肝外组织。