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Effect of Galactooligosaccharide on PPARs/PI3K/Akt Pathway and Gut Microbiota in High-Fat and High-Sugar Diet Combined with STZ-Induced GDM Rat Model

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Abstract

Gestational diabetes mellitus (GDM) is a metabolic disorder, characterized by underlying glucose intolerance, diabetes onset or first diagnosis during pregnancy. Galactooligosaccharide (GOS) is essential for consumer protection as food supplementation. However, there is limited understanding of the effects of GOS on GDM. We successfully established a GDM rat model to explore GOS whether participated in PPARs/PI3K/Akt pathway and gut microbiota metabolites to treat for GDM. In this study, compared with the GDM group, GOS administration lowered the levels of TG, LDL-C, and HDL-C in rat serum, as well as improved the pathological changes pancreatic, liver, and kidney tissues. Compared with the GDM group, the protein expressions of PPARα, PPARγ, and PPARβ/δ markedly enhanced in GOS-treated groups (P < 0.01). Moreover, GOS administration upregulated the protein expressions of PPARα, PPARβ, PPARγ, PI3K, Akt, GLUT4, Bax, and Bcl2. GOS administration altered gut microbiota metabolites, including both SCFAs and BAs. Correlation analysis revealed close relationships between gut microbiota and experimental indicators. This study indicated that GOS effectively improved GDM in rats through the modulation of PPARs/PI3K/Akt pathway and gut microbiota. Thus, the GOS could be recommended as a candidate for novel therapy of GDM.

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All data generated or analyzed during this study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Key R & D Projects of China (Grant No. 2018YFC1704204).

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JW and JZ conceived and drafted the manuscript, prepared figures. JW, JZ, and YH conceived and designed the experiments. JW and JZ performed the animal experiments and analyzed the data. YH, HZ, and JZ (Jieqiong Zeng) reviewed and modified the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Huifen Zhou or Yu He.

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Wan, J., Zhu, J., Zeng, J. et al. Effect of Galactooligosaccharide on PPARs/PI3K/Akt Pathway and Gut Microbiota in High-Fat and High-Sugar Diet Combined with STZ-Induced GDM Rat Model. Probiotics & Antimicro. Prot. (2023). https://doi.org/10.1007/s12602-023-10186-z

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