Nuciferine administration in C57BL/6J mice with gestational diabetes mellitus induced by high-fat diet: the improvement of glycolipid disorders and intestinal dysbacteriosis

Gestational diabetes mellitus (GDM) has become a global health concern as the main result of the contribution to the high risk of adverse pregnancy outcomes for both maternal and fetus. However, there is absence of an ideal and widely acceptable therapy. Nuciferine has previously been shown to exert beneficial effects in various metabolic diseases. This study aimed to investigate the potential therapeutic efficacy of nuciferine on GDM in C57BL/6J mice induced by high-fat diet (HFD), which has not been reported before. Results showed that nuciferine improved glucose intolerance, reduced lipid accumulation and elevated glycogen content within hepatocytes, and diminished placental lipid and glycogen depositions, thus ameliorating glycolipid disorders in GDM mice. Additionally, nuciferine protected against histological degenerations of metabolism-associated critical organs including liver, pancreas, and abdominal adipose. Most interestingly, nuciferine could correct intestinal dysbacteriosis in GDM mice, as evidenced by the elevation of probiotics abundances consisting of Akkermansia, Lactobacillus, and Bifidobacterium, which were all negatively correlated with serum and liver triglyceride (TG) and positively associated with hepatic glycogen, and the reduction of conditional pathogens abundances including Escherichia-Shigella and Staphylococcus, and the latter was positively related to serum and liver TG and negatively linked with liver glycogen. Collectively, these findings suggest nuciferine as food-borne strategy played important roles in the management of GDM.