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探索肥胖与骨质疏松症之间的分子联系:来自计算机模拟分析和甘露糖补充的见解。

Exploring molecular links between obesity and osteoporosis: insights from in-silico analysis and mannose supplementation.

作者信息

James Remya, Vineeth Kumar T V, Koushik Narayan Subramanyam, Payva Febby, Pavithra E Amrisa, Venketesh Sivaramakrishnan, Santhy K S

机构信息

Department of Zoology, St. Joseph's College for Women, Alappuzha, Kerala, 688001, India.

School of Biosciences, Department of Zoology, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, 614043, India.

出版信息

Sci Rep. 2025 Aug 11;15(1):29384. doi: 10.1038/s41598-025-07294-x.

DOI:10.1038/s41598-025-07294-x
PMID:40789846
Abstract

D-mannose, a plant-derived monosaccharide used as a dietary supplement, has shown potential in alleviating obesity symptoms and improving bone loss in mice. Obesity, a known risk factor for osteoporosis (OP), suggests shared molecular pathways between these conditions. This study explores the molecular mechanisms of obesity-induced OP and the potential therapeutic role of mannose supplementation. Using in-silico analysis, GEO2R was applied to dataset GSE110796 to identify differentially expressed genes (DEGs) under high-fat diet-induced obesity and mannose supplementation. Enrichment analysis via Enrichr and ClueGO revealed significant molecular pathways altered by high-fat diets and reversed by mannose. Similarly, pathways for OP were identified using the GEO dataset GSE56815 and DisGeNET-associated genes. Forty-four overlapping pathways were identified between obesity and OP, with key immune and inflammatory pathways modulated by mannose. Notably, genes upregulated in osteoclast differentiation during obesity were downregulated with mannose. These findings suggest that mannose modulates shared pathways in obesity and OP, offering a cost-effective therapeutic approach. This study enhances understanding of obesity-induced OP and provides a foundation for innovative medical interventions.

摘要

D-甘露糖是一种源自植物的单糖,用作膳食补充剂,已显示出在减轻小鼠肥胖症状和改善骨质流失方面的潜力。肥胖是骨质疏松症(OP)的已知风险因素,表明这些病症之间存在共同的分子途径。本研究探讨了肥胖诱导的OP的分子机制以及甘露糖补充剂的潜在治疗作用。通过计算机分析,将GEO2R应用于数据集GSE110796,以鉴定高脂饮食诱导的肥胖和甘露糖补充下的差异表达基因(DEG)。通过Enrichr和ClueGO进行的富集分析揭示了高脂饮食改变并被甘露糖逆转的重要分子途径。同样,使用GEO数据集GSE56815和DisGeNET相关基因鉴定了OP的途径。在肥胖和OP之间鉴定出44条重叠途径,关键的免疫和炎症途径由甘露糖调节。值得注意的是,肥胖期间破骨细胞分化中上调的基因在使用甘露糖后下调。这些发现表明,甘露糖调节肥胖和OP中的共同途径,提供了一种经济有效的治疗方法。本研究增进了对肥胖诱导的OP的理解,并为创新的医学干预措施提供了基础。

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本文引用的文献

1
In-silico analysis predicts disruption of normal angiogenesis as a causative factor in osteoporosis pathogenesis.计算机分析预测,正常血管生成的破坏是骨质疏松症发病机制中的一个致病因素。
BMC Genom Data. 2024 Oct 8;25(1):85. doi: 10.1186/s12863-024-01269-z.
2
Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk.肥胖相关的 T 细胞功能障碍会损害免疫监视并增加癌症风险。
Nat Commun. 2024 Apr 2;15(1):2835. doi: 10.1038/s41467-024-47359-5.
3
Adipose extracellular matrix deposition is an indicator of obesity and metabolic disorders.
脂肪细胞外基质的沉积是肥胖和代谢紊乱的一个指标。
J Nutr Biochem. 2023 Jan;111:109159. doi: 10.1016/j.jnutbio.2022.109159. Epub 2022 Sep 24.
4
D-mannose for preventing and treating urinary tract infections.D-甘露糖防治尿路感染。
Cochrane Database Syst Rev. 2022 Aug 30;8(8):CD013608. doi: 10.1002/14651858.CD013608.pub2.
5
Association of amino acid metabolites with osteoporosis, a metabolomic approach: Bushehr elderly health program.氨基酸代谢物与骨质疏松症的关联:一项代谢组学研究——布什尔老年健康计划。
Metabolomics. 2022 Aug 1;18(8):63. doi: 10.1007/s11306-022-01919-2.
6
Role of Primary Cilia in Skeletal Disorders.原发性纤毛在骨骼疾病中的作用。
Stem Cells Int. 2022 Jun 18;2022:6063423. doi: 10.1155/2022/6063423. eCollection 2022.
7
Osteoporosis Due to Hormone Imbalance: An Overview of the Effects of Estrogen Deficiency and Glucocorticoid Overuse on Bone Turnover.激素失衡导致的骨质疏松症:雌激素缺乏和糖皮质激素过度使用对骨代谢的影响概述。
Int J Mol Sci. 2022 Jan 25;23(3):1376. doi: 10.3390/ijms23031376.
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BMC Cancer. 2022 Feb 9;22(1):157. doi: 10.1186/s12885-022-09253-5.
9
Gut microbiome and its role in colorectal cancer.肠道微生物组及其在结直肠癌中的作用。
BMC Cancer. 2021 Dec 11;21(1):1325. doi: 10.1186/s12885-021-09054-2.
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mBio. 2021 Dec 21;12(6):e0249621. doi: 10.1128/mBio.02496-21. Epub 2021 Nov 2.