Fan Zhirui, Li Lifeng, Li Xiaoli, Zhang Meng, Zhong Yali, Li Yaqing, Yu Dandan, Cao Jing, Zhao Jing, Zhang Mingzhi, Liu Zhangsuo, Goscinski Mariusz Adam, Berge Viktor, Nesland Jahn M, Suo Zhenhe
Department of Oncology, The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan Province China
Department of Pathology, The Third Affiliated Hospital of Zhengzhou University Zhengzhou Henan Province China.
RSC Adv. 2018 May 4;8(30):16636-16644. doi: 10.1039/c8ra00253c. eCollection 2018 May 3.
Although abnormal metabolism in metabolic syndrome and tumours has been well described, the relationship between oxoglutarate dehydrogenase (OGDH) and obesity-related diseases is still largely unknown. This study aimed to investigate whether it was possible to use transcription activator-like effector nuclease (TALEN) technology to establish OGDH rats and then study the effect of a high-fat diet (HFD) on these rats. However, after OGDHrats were generated, we were unable to identify any OGDH rats by performing mating experiments with the OGDH rats for almost one year. During the past three years, only OGDH rats were stably established, and correspondingly reduced OGDH expression in the tissues of the OGDH rats was verified. No significant abnormal behaviour was observed in the OGDH rats compared to the wild-type (WT) control rats. However, the OGDH rats were revealed to have higher body weight, and the difference was even significantly greater under the HFD condition. Furthermore, blood biochemical and tissue histological examinations uncovered no abnormalities with normal diets, but a HFD resulted in liver dysfunction with pathological alterations in the OGDH rats. Our results strongly indicate that OGDH homologous knockout is lethal in rats but heterologous OGDH knockout results in vulnerable liver lesions with a HFD. Therefore, the current study may provide a useful OGDH rat model for further investigations of metabolic syndrome and obesity-related hepatic carcinogenesis.
尽管代谢综合征和肿瘤中的异常代谢已得到充分描述，但氧代戊二酸脱氢酶（OGDH）与肥胖相关疾病之间的关系仍 largely未知。本研究旨在探讨是否有可能使用转录激活样效应核酸酶（TALEN）技术建立OGDH大鼠，然后研究高脂饮食（HFD）对这些大鼠的影响。然而，在产生OGDH大鼠后，我们在近一年的时间里通过与OGDH大鼠进行交配实验，未能鉴定出任何OGDH大鼠。在过去三年中，仅稳定建立了OGDH大鼠，并相应地验证了OGDH大鼠组织中OGDH表达的降低。与野生型（WT）对照大鼠相比，在OGDH大鼠中未观察到明显的异常行为。然而，OGDH大鼠的体重较高，在HFD条件下差异甚至更大。此外，血液生化和组织组织学检查在正常饮食下未发现异常，但HFD导致OGDH大鼠出现肝功能障碍并伴有病理改变。我们的结果强烈表明，OGDH同源敲除在大鼠中是致命的，但异源OGDH敲除在HFD条件下会导致易患肝脏病变。因此，本研究可能为进一步研究代谢综合征和肥胖相关肝癌发生提供有用的OGDH大鼠模型。
