Laboratory of Transgenic Models of Diseases, Division BIOCEV, Institute of Molecular Genetics of the Czech Academy of Sciences, 252 50 Vestec, Czech Republic.
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, and General University Hospital, 128 00 Prague, Czech Republic.
Genes (Basel). 2021 Jul 18;12(7):1087. doi: 10.3390/genes12071087.
Complex metabolic conditions such as type 2 diabetes and obesity result from the interaction of numerous genetic and environmental factors. While the family of Nme proteins has been connected so far mostly to development, proliferation, or ciliary functions, several lines of evidence from human and experimental studies point to the potential involvement of one of its members, NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) in carbohydrate and lipid metabolism. As a complete lack of is semilethal in rats, we compared morphometric, metabolic, and transcriptomic profiles of standard diet-fed heterozygous - on male rats vs. their wild-type controls. - animals showed increased body weight, adiposity, higher insulin levels together with decreased glucose tolerance. Moreover, they displayed pancreatic islet fibrosis and kidney tubular damage. Despite no signs of overt liver steatosis or dyslipidemia, we found significant changes in the hepatic transcriptome of - male rats with a concerted increase of expression of lipogenic enzymes including , , and a decrease of and . Network analyses suggested possible links between and the activation of Srebf1 and Srebf2 upstream regulators. These results further support the implication of NME7 in the pathogenesis of glucose intolerance and adiposity.
复杂的代谢状况，如 2 型糖尿病和肥胖，是由众多遗传和环境因素相互作用的结果。虽然 Nme 蛋白家族迄今主要与发育、增殖或纤毛功能有关，但来自人类和实验研究的几条证据表明，其成员之一 NME7（非转移性细胞 7，核苷二磷酸激酶 7）可能参与碳水化合物和脂质代谢。由于 基因完全缺失的大鼠具有半致死性，我们比较了标准饮食喂养的杂合子 - 雄性大鼠与野生型 对照组的形态计量学、代谢和转录组特征。- 大鼠表现出体重增加、肥胖、胰岛素水平升高，同时葡萄糖耐量降低。此外，它们还表现出胰岛纤维化和肾小管损伤。尽管没有明显的肝脂肪变性或血脂异常迹象，但我们发现 - 雄性大鼠的肝转录组存在显著变化，包括脂肪生成酶的表达协同增加，如 、 、 和 ，而 则减少。网络分析表明 与 Srebf1 和 Srebf2 上游调节因子的激活之间可能存在联系。这些结果进一步支持了 NME7 在葡萄糖耐量和肥胖发病机制中的作用。
