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

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.

ORGANISM(S): Mus musculus

PROVIDER: GSE286364 | GEO | 2025/10/14

REPOSITORIES: GEO

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Project description:To profile the expression of circulating miRNAs in a mouse model of diet-induced obesity (DIO) with subsequent weight-reduction with low-fat diet (LFD), eighteen C57BL/6 male mice were grouped into three subgroups as: (1) Control: the mice fed with the standard AIN-76A (fat: 11.5 kcal%) diet for 12 wks; (2) DIO: the mice fed with 58 kcal% high-fat diet for 12 wks; (3) DIO+LFD: the mice fed with high-fat diet for 8 wks to induce obesity, then changed to 10.5 kcal% low-fat diet for subsequent 4 wks. C57BL/6 mice were purchased from BioLasco (Taipei, Taiwan). All housing conditions were maintained, and surgical procedures, including analgesia, were performed in an Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)-accredited SPF facility according to national and institutional guidelines. In this experiment, eighteen C57BL/6 wild type male mice were randomly grouped into three subgroups (n=6 in each group): (1) Control: the control mice were fed ad libitum a standard AIN-76A (fat: 11.5 kcal%) diet for 12 wks; (2) DIO: the mice were fed ad libitum a 58 kcal% HFD (D12331; Research Diets Inc., New Brunswick, NJ) for 12 wks to induce obesity; (3) DIO+LFD: the mice fed ad libitum a 58 kcal% HFD (D12331) for 8 wks to induce obesity, then continued the feeding of 10.5 kcal% LFD (D 12329; Research Diets Inc.) for additional 4 wks. Weight measurements were performed on a weekly basis to for these three groups of mice. Evaluation of blood glucose levels was performed at the beginning and in the end of the experiment to confirm that the HFD-fed mice developed an obese and insulin resistant phenotype. After the end of experiment at 12w, all mice were killed. The abdominal WAT of each mice was removed and weighted. Paraffin-embedded abdominal WAT was sectioned at 5 M-NM-<m and stained with hematoxylin and eosin to measure mean adipocyte area. A volume of 1 mL of whole blood was collected into a plain tube and allowed to clot for 1 hour. The sera samples were aliquoted after centrifugation at 3,000 M-CM-^W g for 10 minutes and stored at M-bM-^HM-^R80M-BM-0C until further analysis.

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

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