Yang_2023_Arch.Med.Res_55_102925

BACKGROUND AND AIM: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders in pregnancy, and a novel association of maternal lipid profile has been suggested to play an important role. However, the molecular mechanism is not clear. METHODS: Bio-analyzed combined with placental metabonomics and single-cell RNA-sequencing (scRNA-seq) successfully identified a potentially important molecule: alpha-beta hydrolase domain-containing protein 5 (ABHD5). The syncytiotrophoblast (SCT) cell model was adopted as a fusion of BeWo cells in response to forskolin. On this basis, the high glucose-stimulated cell experiment was carried out. 15 women with GDM and 15 normal pregnant women were recruited for validation experiments. RESULTS: ABHD5 was mainly expressed in the trophoblast cells, especially in SCT cells, and significantly decreased in the GDM placenta. After stimulation by high glucose, the expression of ABHD5 was downregulated in a time-dependent manner in BeWo cells treated with forskolin. At the same time, lipid droplets (LDs) were increased in the SCT. LD storage was also increased in the SCT with siABHD5, while it was significantly reduced in SCT cells with high ABHD5 expression. However, this effect could be attenuated by downregulated carnitine palmitoyltransferase 1B (CPT1B). CONCLUSIONS: ABHD5-CPT1B is confirmed as an important regulator of placental lipid metabolism.