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, whereas its potential against GDM-induced liver injury in offspring remains unclear.

OBJECTIVES

The present study aimed to investigate the hepatoprotective effects of maternal SA supplementation in GDM-exposed offspring and to explore its underlying mechanisms.

METHODS

C57BL/6J mice were divided into 3 groups: a control (NC-m) group, a gestational diabetes mellitus (GDM-m) group, and a gestational diabetes mellitus plus SA (GDM+SA-m) group. The GDM-m group was induced using a high-fat diet combined with intraperitoneal streptozotocin 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. Offspring from 3 groups were fed a control diet until 8 wk 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 hematoxylin and eosin staining, aspartate aminotransferase and alanine aminotransferase, oxidative stress markers, inflammatory cytokines, and nontargeted metabolomics.

RESULTS

Compared with the NC-o 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.

CONCLUSIONS

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.