Utility of LPL transgenic rabbits as a human disease model

在本研究中，我们检测了脂蛋白脂肪酶（LPL）转基因家兔在鼠粮或高脂饲料（HFD）负荷下的葡萄糖耐量和胰岛素敏感性。结果总结如下：1。在鼠粮条件下，静脉葡萄糖耐量试验（IVGTT）、胰岛素耐量试验（IVTT）和高血糖钳夹试验显示LPL转基因家兔的胰岛素敏感性升高。在HFD诱导的肥胖状态下，与非转基因家兔相比，LPL的过表达可以阻止内脏脂肪的积累，提高胰岛素敏感性。病理检查显示，LPL转基因家兔脂肪细胞体积小，甘油三酯沉积呈脂肪肝。将LPL转基因家兔与家族性高脂血症动物模型WHHL家兔配种后，LPL转基因WHHL家兔在高脂血症下喂养HFD诱导胰岛素抵抗后，胰岛素敏感性也有所改善。我们的研究结果表明，家兔过表达LPL可能抑制脂肪的积累，改善hfd诱导的肥胖的胰岛素敏感性。这可能是一个有趣的结果，相比之下，在小鼠报道的LPL转基因小鼠表现出而不是胰岛素抵抗。

In this study, we examined glucose tolerance and insulin sensitivity under chow diet or high-fat diet (HFD) loading in lipoprotein lipase (LPL) transgenic rabbits. The results are summarized below.1.Under chow diet condition, intravesous glucose tolerance test (IVGTT), insulin tolerance test (IVTT) and hyper-euglycemic clamp test revealed that LPL transgenic rabbits have increased insulin sensitivity.2.In obese condition induced by HFD feeding, overexpression of LPL prevented accumulation of visceral fat and improved insulin sensitivity compared with non-transgenic control rabbits. Moreover, pathological examination revealed that LPL transgenic rabbit has small adipocytes in size and fatty liver according to the deposition of triglycerides.3.In mating LPL transgenic rabbit with WHHL rabbits which is an animal model for familial hyperlipidemia, LPL transgenic WHHL rabbits also showed amelioration of insulin sensitivity after feeding of HFD to induce insulin resistance according to obesity under hyperlipidemia.These observations in our study suggested that overexpression of LPL in rabbits may inhibit the accumulation of fat and improve the insulin sensitivity under HFD-induced obesity. This can be an interesting results compare with that in the mice reported LPL transgenic mice showed rather than insulin resistance.