Abstract
Gestational diabetes mellitus (GDM) leads to macrosomia primarily due to fat accumulation caused by adipocyte differentiation. This study aims to investigate the role and underlying mechanisms of Chromatin assembly factor 1 subunit A (CHAF1A) in GDM-induced macrosomia. CHAF1A expression was compared between the GDM with macrosomia group (n = 25) and the normal glucose with normal weight group (n = 15), and the correlation between CHAF1A and neonatal body composition was examined. CHAF1A was overexpressed and knocked down in human visceral preadipocytes (HPA-v), and the effects on cell proliferation and adipogenic differentiation were measured, then the expressions of adipogenic markers were determined. Transcriptome sequencing was employed to investigate the potential mechanisms. Placental immunohistochemistry showed that the expression of CHAF1A in the GDM with macrosomia group was significantly higher than that in the control group (P < 0.05). Correlation analysis showed that CHAF1A expression was positively correlated with neonatal weight, body fat percentage, and fat mass. In functional assays, preadipocytes overexpressing CHAF1A showed enhanced proliferation and adipogenic differentiation, while knockdown of CHAF1A resulted in the opposite effect. Moreover, CHAF1A affected the expression of adipogenic markers. Transcriptome sequencing analysis showed that the differentially expressed genes after CHAF1A silencing were enriched in signaling pathways closely related to preadipocyte differentiation and hormone secretion and synthesis, such as JAK-STAT, Wnt and BMP signaling pathways. CHAF1A promotes the proliferation and differentiation of preadipocytes, which may be a direction for exploring fetal fat accumulation leading to macrosomia in GDM.