Sialic Acid Supplementation in Perinatal Mice Attenuates Gestational Diabetes Mellitus-induced Liver Injury in Offspring at Early Adulthood

Background Gestational diabetes mellitus (GDM) is prone to induce hepatic injury in offspring. Sialic acid (SA) exhibits hepatoprotective effects, while its potential against GDM-induced liver injury in offspring remains unclear. Objective The present study aimed to investigate the hepatoprotective effects of maternal sialic acid (SA) supplementation in GDM-exposed offspring and to explore its underlying mechanisms. Methods C57BL/6J mice were divided into three groups: a control (NC-m) group, a gestational diabetes mellitus (GDM-m) group, and a gestational diabetes mellitus plus sialic acid (GDM+SA-m) group. The GDM-m group was induced using high-fat diet combined with intraperitoneal streptozotocin (STZ) injection. The GDM+SA-m group was administered N-glycolylneuraminic acid (Neu5Ac), human milk SA, via intragastric gavage at a dose of 50 mg/kg during pregnancy and lactation. Offsprings from three groups were fed a control diet until 8 weeks of age, with 20, 20, and 19 in the NC-o, GDM-o, and GDM+SA-o groups, respectively. Liver was obtained and analyzed for HE staining, AST and ALT, oxidative stress markers, inflammatory cytokines, and non-targeted metabolomics. Results and Conclusion s: Compared with the NC group, GDM significantly elevated liver transaminase levels and increased inflammatory and oxidative stress in offspring mice, with more pronounced effects observed in males. SA intervention partially attenuated this damage. Concurrently, metabolomic analysis revealed that SA significantly regulated lipid metabolism and taurine/hypotaurine pathways. The results suggested that maternal SA intervention ameliorated GDM-induced offspring liver injury potentially by regulating hepatic lipid and taurine/hypotaurine metabolism, providing a novel mechanistic insight for early-life intervention in GDM.