Utility of LPL transgenic rabbits as a human disease model

在这项研究中，我们研究了脂蛋白脂酶（LPL）转基因兔在普通饲料和高脂饲料（HFD）负荷下的糖耐量和胰岛素敏感性。结果如下：1.普通饲料条件下，膀胱葡萄糖耐量试验（IVGTT）、胰岛素耐量试验（IVTT）和高正葡萄糖钳夹试验均显示LPL转基因兔具有较高的胰岛素敏感性; 2.在HFD诱导的肥胖状态下，与非转基因对照兔相比，LPL过表达可抑制内脏脂肪堆积，提高胰岛素敏感性。LPL转基因兔的脂肪细胞体积较小，脂肪肝组织中脂肪酸沉积较多。3.将LPL转基因兔与家族性高脂血症动物模型WHHL兔交配，LPL转基因WHHL兔在喂食HFD诱导高脂血症下肥胖的胰岛素抵抗后，也表现出胰岛素敏感性的改善。提示过表达LPL可抑制HFD诱导的肥胖兔体内脂肪堆积，提高胰岛素敏感性。这可能是一个有趣的结果相比，在小鼠报告的LPL转基因小鼠显示，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.