TDAG51 通过 SREBP-1/ANGPTL8 通路减轻妊娠期糖尿病中受损的脂代谢和胰岛素抵抗。
TDAG51 Attenuates Impaired Lipid Metabolism and Insulin Resistance in Gestational Diabetes Mellitus Through SREBP-1/ANGPTL8 Pathway.
机构信息
Department of Obstetrics, The First People’s Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi, China
Department of Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
出版信息
Balkan Med J. 2023 May 8;40(3):175-181. doi: 10.4274/balkanmedj.galenos.2023.2022-8-61. Epub 2023 Mar 24.
BACKGROUND
T-cell death-associated gene 51 (TDAG51) belongs to the transcription factor family and is involved in the energy homeostasis of the liver through the regulation of lipogenesis.
AIMS
To evaluate the role of T-cell death-associated gene 51 in gestational diabetes mellitus.
STUDY DESIGN
Experimental animal and human-sample study.
METHODS
A total of 30 patients with GDM were enrolled in the study. TDAG51 expression in patients with gestational diabetes mellitus was assessed by Western blotting and quantitative reverse-transcription polymerase chain reaction. A high-fat and high-sugar diet was used to establish a gestational diabetes mellitus model. Mice with gestational diabetes were injected with lentivirus-mediated overexpression of TDAG51. Blood glucose was measured using a glucometer, and glucose and insulin tolerance tests were performed to detect insulin resistance. Liver and adipose tissues were subjected to hematoxylin-eosin staining. Cell apoptosis was detected by TUNEL staining. Human villous trophoblast cells (HTR-8/SVneo) were treated with a high-glucose medium to induce gestational diabetes mellitus.
RESULTS
TDAG51 was downregulated in gestational diabetes mellitus and high glucose-induced HTR-8/SVneo. TDAG51 overexpression reduced the level of blood glucose, enhanced serum insulin, and attenuated glucose and insulin tolerance in gestational diabetes mellitus mice. TDAG51 overexpression also ameliorated impaired lipid metabolism and alleviated adipocyte hypertrophy and hepatic lipid droplets in gestational diabetes mellitus mice. The expressions of SREBP-1 and ANGPTL8 were upregulated in gestational diabetes mellitus and showed a negative correlation with TDAG51 in patients with gestational diabetes mellitus. TDAG51 increased the expressions of SREBP-1 and ANGPTL8 in gestational diabetes mellitus mice. TDAG51 overexpression reduced cell apoptosis and enhanced cell viability of high glucose-induced HTR-8/SVneo. Ectopic expression of ANGPTL8 attenuated the TDAG51-induced increase in cell viability and decrease in apoptosis in high glucose-induced HTR-8/SVneo.
CONCLUSION
TDAG51 alleviated impaired lipid metabolism and insulin resistance in gestational diabetes mellitus via downregulation of SREBP 1/ANGPTL8 pathway.
背景
T 细胞死亡相关基因 51（TDAG51）属于转录因子家族，通过调节脂肪生成参与肝脏的能量稳态。
目的
评估 T 细胞死亡相关基因 51 在妊娠糖尿病中的作用。
研究设计
实验动物和人体样本研究。
方法
本研究共纳入 30 例 GDM 患者。通过 Western blot 和定量逆转录聚合酶链反应评估妊娠糖尿病患者 TDAG51 的表达。采用高脂肪高糖饮食建立妊娠糖尿病模型。用慢病毒介导的 TDAG51 过表达对妊娠糖尿病小鼠进行注射。使用血糖仪测量血糖，进行葡萄糖和胰岛素耐量试验以检测胰岛素抵抗。对肝和脂肪组织进行苏木精-伊红染色。通过 TUNEL 染色检测细胞凋亡。用高糖培养基处理人绒毛滋养层细胞（HTR-8/SVneo）以诱导妊娠糖尿病。
结果
TDAG51 在妊娠糖尿病和高糖诱导的 HTR-8/SVneo 中表达下调。TDAG51 过表达降低了血糖水平，增强了血清胰岛素，并改善了妊娠糖尿病小鼠的葡萄糖和胰岛素耐量。TDAG51 过表达还改善了受损的脂质代谢，减轻了妊娠糖尿病小鼠的脂肪细胞肥大和肝内脂质滴。SREBP-1 和 ANGPTL8 的表达在妊娠糖尿病中上调，并与妊娠糖尿病患者的 TDAG51 呈负相关。TDAG51 增加了妊娠糖尿病小鼠中 SREBP-1 和 ANGPTL8 的表达。TDAG51 过表达降低了高糖诱导的 HTR-8/SVneo 中的细胞凋亡并增加了细胞活力。ANGPTL8 的异位表达减弱了 TDAG51 诱导的高糖诱导的 HTR-8/SVneo 中细胞活力的增加和凋亡的减少。
结论
TDAG51 通过下调 SREBP1/ANGPTL8 通路缓解妊娠糖尿病中的脂质代谢和胰岛素抵抗。
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