Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China.
College of Food Science, Northeast Agricultural University, Harbin 150030, China.
Nutrients. 2020 Apr 17;12(4):1116. doi: 10.3390/nu12041116.
Lactoferrin (LF) exerts a promoting bone health function. The effects of LF on bone formation at the metabolic level have been less explored. Urinary metabolic profiling of growing Sprague-Dawley (SD) rats LF-supplemented (1000 mg/kg bw) for four weeks were explored by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The serum markers of bone formation and bone resorption, the bone mass, and the osteogenesis markers of femur were measured by an enzyme-linked immunosorbent assay, micro-computerized tomography, and immunohistochemistry, respectively. Compared with the control, LF supplementation improved bone formation ( < 0.05), reduced bone resorption ( < 0.05), enhanced femoral bone mineral density and microarchitecture ( < 0.05), and upregulated osteocalcin, osterix, and Runx-2 expression ( < 0.05) of femur. LF upregulated 69 urinary metabolites. KEGG and pathway enrichment analyses of those urinary metabolites, and the Person's correlation analyses among those urinary metabolites and bone status revealed that LF impacted on bone formation via regulatory comprehensive pathways including taurine and hypotaurine metabolism, arginine and proline metabolism, cyanoamino acid metabolism, nitrogen metabolism, nicotinate and nicotinamide metabolism, and fatty acid biosynthesis. The present study indicated the metabolomics is a useful and practical tool to elucidate the mechanisms by which LF augments bone mass formation in growing animals.
乳铁蛋白（LF）具有促进骨骼健康的功能。然而，LF 对代谢水平上的成骨作用的影响仍较少被探索。本研究采用液相色谱-串联质谱（LC-MS/MS）技术，对补充 LF（1000mg/kg bw）4 周的生长型 Sprague-Dawley（SD）大鼠的尿液代谢物进行了分析。通过酶联免疫吸附试验、微计算机断层扫描和免疫组织化学分别检测了血清骨形成和骨吸收标志物、股骨骨量和成骨标志物。与对照组相比，LF 补充剂改善了骨形成（<0.05），减少了骨吸收（<0.05），增强了股骨骨矿物质密度和微结构（<0.05），并上调了股骨的骨钙素、成骨特异性转录因子 2（Runx-2）和osterix 的表达（<0.05）。LF 上调了 69 种尿液代谢物。KEGG 和途径富集分析以及这些尿液代谢物与骨状态之间的 Person 相关性分析表明，LF 通过调节包括牛磺酸和次牛磺酸代谢、精氨酸和脯氨酸代谢、氰基氨基酸代谢、氮代谢、烟酰胺和烟酸代谢以及脂肪酸生物合成等综合途径影响骨形成。本研究表明代谢组学是一种有用且实用的工具，可阐明 LF 增加生长动物骨量形成的机制。
