Nesfatin-1 Alleviates High Glucose/high Lipid-induced Injury of Trophoblast Cells During Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is a common disease in pregnant women, imposing risks on both mother and fetus. Dysregulated nesfatin-1 has been observed in women with GDM, but the specific role of nesfatin-1 underlying the pathological process of GDM is unclear. The main objective of this study is to investigate the role and the molecular mechanism of nesfatin-1 in GDM. HTR-8/SVneo cells were treated with high glucose (HG)/high lipid (HL) to mimic the injured trophoblast of GDM in vitro. Cell viability, cytotoxicity and apoptosis were measured using CCK-8, LDH and TUNEL assays, respectively. The levels of inflammatory cytokines and antioxidant factors were detected using their commercial kits. ATP level and cytochrome c were determined with corresponding detecting kits. Quantitative real-time PCR and Western blot were performed to detect the expression of corresponding genes. The results showed that nesfatin-1 was downregulated upon HG/HL stimulation. Nesfatin-1 treatment greatly alleviated HG/HL-induced cell viability loss, cytotoxicity, inflammatory response, oxidative stress, and apoptosis in HTR-8/SVneo cells. In addition, nesfatin-1 promoted ATP generation, reduced the leakage of cytochrome c from mitochondria to cytoplasm, and upregulated mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1), alleviating mitochondrial dysfunction. Furthermore, nesfatin-1 inhibited p38 MAPK signaling. p79350, an agonist of p38 MAPK signaling, remarkably hindered the protective role of nesfatin-1 in HG/HL-induced HTR-8/SVneo cells. In conclusion, nesfatin-1 exerted a protective effect on GDM model in vitro, by regulating p38 MAPK signaling pathway, providing novel insights of treating GDM.