Glutamine: A novel player in maintaining skeletal strength and body fitness in obese mice

IF 7.4 2区医学 Q1 NUTRITION & DIETETICS

Clinical nutrition Pub Date : 2025-10-09 DOI:10.1016/j.clnu.2025.09.018

Martina Dzubanova , Michaela Ferencakova , Dung K. Nguyen , Kristina Bardova , Elena Golovina , Heleen Fehervary , Andrea Benova , Yusuf Odabaşı , Ravindra Naraine , Radek Sindelka , Frantisek Spoutil , Jan Prochazka , Tomas Cajka , G. Harry van Lenthe , Rita Sarkis , Olaia Naveiras , Martin Rossmeisl , Jan Kopecky , Michaela Tencerova

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Abstract

Background and aims

Glutamine plays a key role in cellular metabolism and tissue homeostasis. In obesity, circulating glutamine levels decline, accompanied by impaired bone homeostasis and increased fracture risk. While dietary glutamine supplementation shows metabolic benefits, its effects on bone and fat metabolism remain unclear. This study investigates whether glutamine supplementation mitigates obesity-induced alterations in bone and fat metabolism.

Methods

C57BL/6J male mice were subjected to a 2-month dietary intervention with either high-fat diet (HFD) or HFD supplemented with glutamine (HFD + G) and low-fat diet (LFD) as a control group. Body weight, fat mass, glucose tolerance, white adipose tissue (WAT) morphology, and bone parameters were analyzed. Functional assays of adipose-derived mesenchymal stem cells (AT-MSCs) and bone marrow stromal cells (BMSCs) assessed metabolic phenotype and differentiation potential. Glutamine turnover was evaluated, and findings were extended to human BMSCs to assess sex-specific patterns of glutaminolysis.

Results

Glutamine supplementation attenuated body weight gain, fat mass, and WAT weight, along with improved glucose tolerance compared to HFD-fed mice. In WAT, glutamine reduced adipocyte hypertrophy and inflammation, while in AT-MSCs it suppressed obesity-driven hyper-metabolic phenotype by shifting cells toward quiescence. In bone, glutamine improved bone quality, along with reduced bone marrow adiposity and decreased bone resorption. BMSCs from glutamine-treated mice showed decreased adipogenic and increased osteogenic potential, supported by enhanced glutamine turnover, which maintained the stemness of the cells and reduced the inflammation induced by obesity. In human BMSCs, glutamine metabolism displayed sex-specific differences, underscoring its physiological relevance.

Conclusion

Glutamine supplementation improves systemic metabolic health and bone integrity at both the organ and cellular levels, highlighting its potential as a therapeutic strategy for preventing obesity-related metabolic and bone diseases.

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谷氨酰胺：维持肥胖小鼠骨骼力量和身体健康的新角色。

背景与目的：谷氨酰胺在细胞代谢和组织稳态中起关键作用。在肥胖患者中，循环谷氨酰胺水平下降，并伴有骨稳态受损和骨折风险增加。虽然膳食补充谷氨酰胺显示出代谢益处，但其对骨骼和脂肪代谢的影响尚不清楚。本研究探讨补充谷氨酰胺是否能减轻肥胖引起的骨和脂肪代谢的改变。方法：对C57BL/6J雄性小鼠进行为期2个月的饮食干预，以高脂饮食（HFD）或高脂饮食加谷氨酰胺（HFD + G）和低脂饮食（LFD）为对照组。分析体重、脂肪量、葡萄糖耐量、白色脂肪组织（WAT）形态和骨骼参数。脂肪来源的间充质干细胞（AT-MSCs）和骨髓基质细胞（BMSCs）的功能分析评估了代谢表型和分化潜力。评估谷氨酰胺的转化，并将研究结果扩展到人类骨髓间充质干细胞，以评估谷氨酰胺溶解的性别特异性模式。结果：与饲喂hfd的小鼠相比，补充谷氨酰胺可以减轻体重增加、脂肪量和WAT重量，并改善葡萄糖耐量。在WAT中，谷氨酰胺减少脂肪细胞肥大和炎症，而在AT-MSCs中，它通过将细胞转向静止来抑制肥胖驱动的高代谢表型。在骨中，谷氨酰胺改善骨质量，减少骨髓脂肪和减少骨吸收。谷氨酰胺处理小鼠的骨髓间充质干细胞显示出减少的脂肪生成和增加的成骨潜力，这是由于谷氨酰胺的增加，维持了细胞的干性并减少了肥胖引起的炎症。在人骨髓间充质干细胞中，谷氨酰胺代谢表现出性别特异性差异，强调了其生理相关性。结论：补充谷氨酰胺可在器官和细胞水平上改善全身代谢健康和骨骼完整性，突出其作为预防肥胖相关代谢和骨骼疾病的治疗策略的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical nutrition 医学-营养学

CiteScore

14.10

自引率

6.30%

发文量

356

审稿时长

28 days

期刊介绍： Clinical Nutrition, the official journal of ESPEN, The European Society for Clinical Nutrition and Metabolism, is an international journal providing essential scientific information on nutritional and metabolic care and the relationship between nutrition and disease both in the setting of basic science and clinical practice. Published bi-monthly, each issue combines original articles and reviews providing an invaluable reference for any specialist concerned with these fields.