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低聚半乳糖对高脂高糖饮食联合链脲佐菌素诱导的妊娠期糖尿病大鼠模型中PPARs/PI3K/Akt信号通路及肠道菌群的影响

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.

作者信息

Wan Jiayang, Zhu Jiaqi, Zeng Jieqiong, Zhou Huifen, He Yu

机构信息

The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

School of Basic Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Probiotics Antimicrob Proteins. 2025 Apr;17(2):888-902. doi: 10.1007/s12602-023-10186-z. Epub 2023 Nov 13.

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.

摘要

妊娠期糖尿病(GDM)是一种代谢紊乱疾病,其特征为潜在的葡萄糖不耐受、孕期糖尿病发病或首次诊断出糖尿病。低聚半乳糖(GOS)作为食品补充剂对消费者保护至关重要。然而,人们对GOS对GDM的影响了解有限。我们成功建立了GDM大鼠模型,以探究GOS是否通过参与PPARs/PI3K/Akt通路及肠道微生物群代谢产物来治疗GDM。在本研究中,与GDM组相比,给予GOS降低了大鼠血清中TG、LDL-C和HDL-C的水平,并改善了胰腺、肝脏和肾脏组织的病理变化。与GDM组相比,GOS治疗组中PPARα、PPARγ和PPARβ/δ的蛋白表达显著增强(P < 0.01)。此外,给予GOS上调了PPARα、PPARβ、PPARγ、PI3K、Akt、GLUT4、Bax和Bcl2的蛋白表达。给予GOS改变了肠道微生物群代谢产物,包括短链脂肪酸(SCFAs)和胆汁酸(BAs)。相关性分析揭示了肠道微生物群与实验指标之间的密切关系。本研究表明,GOS通过调节PPARs/PI3K/Akt通路和肠道微生物群有效改善了大鼠的GDM。因此,GOS可被推荐作为GDM新型治疗的候选药物。

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