Degraded sweet corn cob polysaccharides modulate T2DM-induced abnormalities in hepatic lipid metabolism via the bile acid-related FXR-SHP and FXR-FGF15-FGFR4 pathways

IF 4.8 1区 农林科学 Q1 FOOD SCIENCE & TECHNOLOGY Food Bioscience Pub Date : 2024-09-10 DOI:10.1016/j.fbio.2024.105085
Weiye Xiu, Xin Wang, Zhiguo Na, Shiyou Yu, Chenchen Li, Jingyang Wang, Mengyuan Yang, Chenxi Yang, Yongqiang Ma
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Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by dysregulation of glucose and lipid metabolism. This study aimed to elucidate the mechanism through which a degraded sweet corn cob polysaccharide (UE-DSCCP-A) mitigates T2DM by modulating hepatic lipid metabolism. Biochemical indices pertinent to lipid metabolism were assessed, and liver pathology was examined in T2DM mice following UE-DSCCP-A treatment. Additionally, metabolomics, PCR, and Western blot analyses were employed to investigate the underlying mechanisms involved. These findings indicated that UE-DSCCP-A ameliorated hepatic lipid metabolism disorders, decreased lipid accumulation, and mitigated hepatic fibrosis. Untargeted metabolomics analysis revealed that UE-DSCCP-A modulated pathways associated with steroid biosynthesis and bile acid synthesis and metabolism in T2DM mice. The bile acid assay results demonstrated that UE-DSCCP-A treatment reduced bile acid levels in both the serum and liver but increased fecal bile acid levels in T2DM mice. Furthermore, alterations in bile acid distribution within the liver were observed. UE-DSCCP-A has the capacity to activate the hepatic FXR-SHP pathway as well as the gut-liver axis involving FXR-FGF15-FGFR4 signaling. Consequently, UE-DSCCP-A is capable of modulating critical target genes and proteins associated with bile acid synthesis and metabolism, regulating steroid biosynthesis, and influencing bile acid synthesis and transport within the liver. Additionally, it has beneficial effects on lipid metabolism disorders in individuals with T2DM. Thus, UE-DSCCP-A represents a promising candidate for functional foods with inherent hypoglycemic properties.

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降解甜玉米棒多糖通过胆汁酸相关的 FXR-SHP 和 FXR-FGF15-FGFR4 通路调节 T2DM 诱导的肝脂代谢异常
2 型糖尿病(T2DM)是一种以糖和脂代谢失调为特征的代谢性疾病。本研究旨在阐明降解甜玉米棒多糖(UE-DSCCP-A)通过调节肝脏脂质代谢缓解 T2DM 的机制。评估了与脂质代谢相关的生化指标,并检查了 UE-DSCCP-A 治疗后 T2DM 小鼠的肝脏病理学。此外,还采用了代谢组学、PCR 和 Western 印迹分析来研究其中的潜在机制。这些研究结果表明,UE-DSCCP-A 能改善肝脏脂质代谢紊乱,减少脂质蓄积,减轻肝纤维化。非靶向代谢组学分析表明,UE-DSCCP-A 调节了 T2DM 小鼠体内与类固醇生物合成和胆汁酸合成代谢相关的通路。胆汁酸测定结果表明,UE-DSCCP-A 治疗降低了 T2DM 小鼠血清和肝脏中的胆汁酸水平,但增加了粪便中的胆汁酸水平。此外,还观察到胆汁酸在肝脏内的分布发生了改变。UE-DSCCP-A 能够激活肝脏 FXR-SHP 通路以及涉及 FXR-FGF15-FGFR4 信号转导的肠肝轴。因此,UE-DSCCP-A 能够调节与胆汁酸合成和代谢相关的关键靶基因和蛋白质,调节类固醇的生物合成,并影响肝脏内胆汁酸的合成和转运。此外,它对 T2DM 患者的脂质代谢紊乱也有益处。因此,UE-DSCCP-A 是具有固有降糖特性的功能食品的理想候选品种。
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来源期刊
Food Bioscience
Food Bioscience Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
6.40
自引率
5.80%
发文量
671
审稿时长
27 days
期刊介绍: Food Bioscience is a peer-reviewed journal that aims to provide a forum for recent developments in the field of bio-related food research. The journal focuses on both fundamental and applied research worldwide, with special attention to ethnic and cultural aspects of food bioresearch.
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