Ma Ya-Hong, Yu Caiguo, Kayoumu Abudurexiti, Guo Xin, Ji Zhili, Liu George
Department of Endocrinology, Beijing Puren Hospital, Beijing, China;
Institute of Cardiovascular Sciences, Peking University and Key Laboratory of Cardiovascular Sciences, Administration of Education, Beijing, China; ; Department of Endocrinology, Luhe Teaching Hospital of Capital Medical University, Beijing;
J Biomed Res. 2015 Apr;29(2):125-31. doi: 10.7555/JBR.29.20140139. Epub 2015 Mar 13.
Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring: maternal non-transgenic control and maternal transgenic offspring, and paternal control and paternal transgenic offspring. Plasma triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG) and fasting insulin (FINS) were measured. ApoCIII overexpression caused severe hypertriglyceridemia, but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups. The 4 groups of offspring had similar birth weight and growth rate. The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice, but there was no difference in plasma TG between maternal and paternal transgenic offspring. Although the FPG of the 4 groups of animals had no difference, the maternal transgenic mice showed impaired glucose tolerance, increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups. In conclusion, maternally inherited hypertriglyceridemia in ApoCIII transgenic mice displayed impaired glucose tolerance, hyperinsulinemia and increased HOMA-R, while paternally inherited hypertriglyceridemia did not have such impacts.
母系遗传的家族性高胆固醇血症（FH）对葡萄糖代谢的损害以及对后代心血管风险的增加程度大于父系遗传的FH。然而，高甘油三酯血症是否通过遗传影响葡萄糖代谢仍不清楚。在本研究中，我们试图比较母系和父系遗传的高甘油三酯血症对小鼠葡萄糖和脂质代谢的影响。将患有严重高甘油三酯血症的载脂蛋白CIII转基因小鼠与非转基因对照小鼠交配，以，以获得4种类型的后代：母系非转基因对照和母系转基因后代，以及父系对照和父系转基因后代。测量血浆甘油三酯（TG）、总胆固醇（TC）、空腹血糖（FPG）和空腹胰岛素（FINS）。载脂蛋白CIII的过表达导致严重的高甘油三酯血症，但转基因雌性小鼠的生育能力未改变，妊娠和产仔正常。4组后代的出生体重和生长速率相似。母系和父系转基因后代的血浆TG比母系和父系对照小鼠高近40倍，但母系和父系转基因后代之间的血浆TG没有差异。虽然4组动物的FPG没有差异，但与其他3组相比，母系转基因小鼠表现出葡萄糖耐量受损、FINS水平升高和更高的稳态模型评估胰岛素抵抗指数（HOMA-IR）。总之，载脂蛋白CIII转基因小鼠中母系遗传的高甘油三酯血症表现出葡萄糖耐量受损、高胰岛素血症和HOMA-R增加，而父系遗传的高甘油三酯血症没有这些影响。
