TDAG51 Attenuates Impaired Lipid Metabolism and Insulin Resistance in Gestational Diabetes Mellitus Through SREBP-1/ANGPTL8 Pathway

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.