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Introduction: Intestinal dysfunction induced by weaning stress is common during breastfeeding period. Docosahexaenoic acid (DHA) is well known for promoting visual and brain development, but its effects on early intestinal development remain unknown. This study investigated the impact of maternal DHA supplementation during lactation on intestinal glucose absorption and gut microbiota in weaning offspring mice. Materials and methods: Dams were supplemented with vehicle (control), 150 mg/(kg body weight · day) DHA (L-DHA), or 450 mg/(kg body weight · day) DHA (H-DHA) throughout lactation by oral administration. After weaning, pups were randomly divided into three groups for athletic analysis, microbial and proteomic analysis, biochemical analysis, 4-deoxy-4-fluoro-D-glucose (4-FDG) absorption test, and gene expression quantitation of glucose transport-associated proteins and mTOR signaling components. Results: The H-DHA group exhibited enhanced grip strength and prolonged swimming duration compared to the control group. Additionally, there were significant increases in jejunal and ileal villus height, and expanded surface area of jejunal villi in the H-DHA group. Microbial analyses revealed that maternal DHA intake increased the abundance of beneficial gut bacteria and promoted metabolic pathways linked to carbohydrate and energy metabolism. Proteomic studies indicated an increased abundance of nutrient transport proteins and enrichment of pathways involved in absorption and digestion in the H-DHA group. This group also showed higher concentrations of glucose in the jejunum and ileum, as well as elevated glycogen levels in the liver and muscles, in contrast to lower glucose levels in the intestinal contents and feces compared to the control group. The 4-FDG absorption test showed more efficient absorption after oral 4-FDG gavage in the H-DHA group. Moreover, the expressions of glucose transport-associated proteins, GLUT2 and SGLT1, and the activation of mTOR pathway were enhanced in the H-DHA group compared to the control group. The L-DHA group also showed similar but less pronounced improvements in these aspects relative to the H-DHA group. Conclusion: Our findings suggested that maternal DHA supplementation during lactation improves the exercise performance, enhances the intestinal glucose absorption by increasing the expressions of glucose transporters, and beneficially alters the structure of gut microbiome in weaning offspring mice.
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Mfge8, a secreted glycoprotein, is a key molecule that mediates the phagocytosis of apoptotic cells. Previous research reported that Mfge8 is critical for the proliferation and differentiation of radial glial cells (RGCs) in the dentate gyrus of adult mice. The treatment of Mfge8 is also beneficial for the repair of central nervous system (CNS) injury after cerebral ischemia. This study aimed to investigate whether the expression of mfge8a in zebrafish embryos was associated with the development of CNS and larval behavior. We found that zebrafish mfge8a was initially expressed at 48 hpf, and its expression was gradually increased in the ventricular zone. Knocking down mfge8a with antisense morpholino oligonucleotides impaired both spontaneous and photoinduced swimming locomotion in the behavioral tests. The neurogenesis analysis in telencephalon showed that mfge8a morphants excessively promoted neural differentiation over self-renewal after RGCs division, and consequently depleted proliferative RGC population during early neurogenesis. Furthermore, downregulation of mfge8a was shown to alter the expression patterns of genes associated with Notch signaling pathway. Our results demonstrated that mfge8a is involved in the maintenance of the progenitor identity of RGCs in embryonic zebrafish brain through regulating Notch signaling pathway, thereby contributing to consistent neurogenesis and locomotor development.
