烟酰胺核苷酸转氢酶基因突变对C57BL／6小鼠糖代谢稳态的影响

Influence of NNT mutation on glucose homeostasis in C57BL/6 mice

目的探讨烟酰胺核苷酸转氢酶（NNT）基因突变对于C57BL/6小鼠糖代谢稳态的影响。方法将无NNT突变的野生型C57BL/6N与携带NNT突变C57BL/6J小鼠交配，F1代杂合小鼠继续交配，得到NNT纯合野生型，NNT纯合突变型，及NNT突变杂合子3种不同NNT基因型的F2代。小鼠4周龄起分别给予高脂饮食或对照饮食4周，每周监测小鼠体重。在小鼠8周时称重，并通过经腹糖耐量试验（IPGTT）检测小鼠糖代谢水平，通过经腹胰岛素耐量试验（ITT）检测小鼠胰岛素敏感性。结果正常饮食或高脂饮食喂养4周后，不同F2代小鼠基因型三者体重并无差异，但是NNT突变小鼠糖耐量显著受损，并且在高脂饮食诱导下NNT突变小鼠胰岛素敏感性相对NNT野生型显著下降。而NNT杂合子小鼠糖代谢及胰岛素敏感性异常不显著。结论NNT基因突变对C57BL/6小鼠的糖代谢表型具有重要影响，杂合突变和纯合突变表型迥异。C57BL/6J和C57BL/6N小鼠不同遗传背景对高脂饮食有不同反应，这是在进行实验设计时需要充分考虑的因素，可能与不同NNT基因型有关。在研究代谢的实验中尽量保持受试小鼠遗传背景的一致，将对实验结果的解释具有重要作用。

ObjectiveTo explore the effect of nicotinaide nucleotide transhydrogenase（NNT） mutation on glucose homeostasis in C57BL/6 mice with mix background.MethodsWe generated wild type NNT homozygous, mutant NNT homozygous and heterozygous by mating the C57BL/6J （with NNT mutation） and 6N （without NNT mutation）. At the age of 4 weeks, those mice were randomly assigned to normal control diet（NCD） or high-fat diet（HFD） for 4 weeks. The body weight was measured every week. At the age of 8 weeks, an intraperitoneal glucose tolerance test（IPGTT） and an intraperitoneal insulin tolerance test （ITT） were performed.ResultsThe body weight growth was not affected by NNT mutation during an HFD fed. NNT mutant mice showed significant glucose intolerance. After 4 weeks of high fat diet, the NNT mutant mice showed a decreased insulin sensitivity, while the glucose excursion curve was not elevated in the heterozygous mice. ConclusionNNT mutation had a significant influence on the phenotype of glucose metabolism and insulin resistance of mice, in particular under a metabolic stress. The phenotypes of heterozygous and homozygous mutant ones differed from each other. When using mice with C57BL/6J and C57BL/6N mixed background in research, NNT mutation should be carefully screened in all metabolic studies.