Branched-chain amino acid metabolic disorder promotes osteoporosis by inhibiting HIF1-α-mediated glycolytic reprogramming in osteoblasts

IF 4 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2025-05-15 DOI:10.1016/j.jff.2025.106885

Xintong Xie , Xue Zhang , Guangliang Wei , Xiping Zhou , Huidong Chen , Zhenboyang Tang , Xiru Lin , Chunyan Huang , Jiqiang Wu , Ping Wang , Chengsong He , Yue He , Jie Chen

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Abstract

Osteoporosis is the leading cause of fractures in the elderly, and metabolic changes, including elevated levels of branched-chain amino acids (BCAAs), have been implicated in its pathogenesis. This study explores the impact of high BCAAs levels on bone health. After feeding mice a diet containing twice the normal BCAAs levels for six months, serum BCAAs levels were elevated, and trabecular bone density decreased. In vivo experiments revealed that high concentrations of BCAAs adversely affected the microstructure of bone in mice, and further targeted metabolomics analysis suggested impaired energy metabolism, potentially associated with “carbohydrate digestion and absorption,” “starch and sucrose metabolism,” and “riboflavin metabolism.” In vitro experiments showed that BCAAs inhibited the proliferation, osteogenic differentiation, and glycolysis of MC3T3-E1 cells, possibly through the regulation of HIF-1α and GLUT1. Excessive BCAAs may reduce bone mass and increase the risk of osteoporosis.

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支链氨基酸代谢紊乱通过抑制HIF1-α-介导的成骨细胞糖酵解重编程促进骨质疏松

骨质疏松是老年人骨折的主要原因，代谢变化，包括支链氨基酸（BCAAs）水平升高，与其发病机制有关。本研究探讨了高支链氨基酸水平对骨骼健康的影响。给小鼠喂食含有两倍于正常BCAAs水平的饮食6个月后，血清BCAAs水平升高，小梁骨密度下降。体内实验显示，高浓度的支链氨基酸对小鼠骨骼的微观结构有不利影响，进一步的靶向代谢组学分析表明，能量代谢受损，可能与“碳水化合物消化和吸收”、“淀粉和蔗糖代谢”以及“核黄素代谢”有关。体外实验表明，BCAAs可能通过调控HIF-1α和GLUT1抑制MC3T3-E1细胞的增殖、成骨分化和糖酵解。过量的支链氨基酸可能会降低骨量，增加骨质疏松症的风险。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.