The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice.
The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice.
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DOI：
10.1096/fj.201600921rr
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Minihane AM
中科院分区：
文献类型：
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作者：
Slim KE;Vauzour D;Tejera N;Voshol PJ;Cassidy A;Minihane AM
我们在小鼠模型中研究了常见的APOE基因型和海洋n-3多不饱和脂肪酸（PUFAs）对肥胖和相关心脏代谢功能障碍的发展的独立和相互作用的影响。将人APOE 3和APOE 4靶向替代小鼠喂食对照高脂饮食（HFD）或补充有来自鱼油的3%n-3 PUFA的HFD（HFD + FO）8周。我们确定了干预对食物摄入、体重和内脏脂肪组织（VAT）质量的影响;血浆、脂质（胆固醇和甘油三酯）、肝酶和脂肪因子;腹膜内葡萄糖耐量试验期间的葡萄糖和胰岛素;以及VAT中Glut 4和ApoE表达。与APOE 4小鼠相比，HFD喂养诱导APOE 3小鼠的体重增加和血脂升高（P < 0.05），沿着胰岛素升高2倍，葡萄糖耐量受损。补充APOE 3而非APOE 4，饮食中添加n-3 PUFA的动物体重增加、血脂和胰岛素降低（P < 0.05），葡萄糖耐量改善，这与VAT Glut 4 mRNA水平增加相关（P < 0.05）。我们的研究结果表明，APOE 3基因型易使小鼠患肥胖症及其代谢并发症，这是由n-3 PUFA补充减弱。斯利姆，K。E、Vauzour，D.，Tejera，N.，沃肖尔，P. J.，卡西迪，A.，Minihane，A. M.膳食鱼油对体重增加和胰岛素敏感性的影响取决于人源化靶向替代小鼠中的APOE基因型。
We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFAs) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a control high-fat diet (HFD) or an HFD supplemented with 3% n-3 PUFAs from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, body weight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; and Glut4 and ApoE expression in VAT. HFD feeding induced more weight gain and higher plasma lipids in APOE3 compared to APOE4 mice (P < 0.05), along with a 2-fold higher insulin and impaired glucose tolerance. Supplementing APOE3, but not APOE4, animals with dietary n-3 PUFAs decreased body-weight gain, plasma lipids, and insulin (P < 0.05) and improved glucose tolerance, which was associated with increased VAT Glut4 mRNA levels (P < 0.05). Our findings demonstrate that an APOE3 genotype predisposes mice to develop obesity and its metabolic complications, which was attenuated by n-3 PUFA supplementation.—Slim, K. E., Vauzour, D., Tejera, N., Voshol, P. J., Cassidy, A., Minihane, A. M. The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice.