Glutamine: A Novel Player in Maintaining Skeletal Strength and Body Fitness in Obese Mice

ABSTRACT: Glutamine plays a key role in cellular metabolism and tissue homeostasis. In obesity, circulating glutamine levels are decreased, accompanied by impaired bone homeostasis and increased fracture risk. While glutamine supplementation in diet has shown metabolic benefits, the mechanisms behind its effects on bone and fat metabolism are not fully understood. This study investigates whether glutamine supplementation may delay the negative impact of obesity on bone and fat metabolism in mice fed a high-fat diet (HFD). Two-month-long dietary intervention in C57BL/6J male mice showed that glutamine supplementantion reduced body weight gain, fat mass, and white adipose tissue (WAT) weight, along with improved glucose tolerance compared to HFD-fed mice. In peripheral WAT, glutamine supplementation improved WAT funcion, as indicated by decreased adipocyte hypertrophy and inflammatory status. Furthermore, glutamine reduced the obesity-driven hyper-metabolic phenotype in primary adipose-derived mesenchymal stem cells by shifting the cells toward a quiescent metabolic state. In bone, glutamine supplementation improved bone quality and microarchitecture, along with reduced bone marrow adiposity and decreased bone resorption in glutamine-treated mice compared to HFD-fed mice. These changes were confirmed by decreased adipogenic and increased osteogenic potential of bone marrow stromal cells isolated from glutamine-treated mice. This was further supported by enhanced glutamine turnover, which maintained the stemness of the cells and reduced the inflammatory status induced by obesity, The importance of glutamine metabolism was also confirmed in human stem cells, showing a sex-specific pattern of glutaminolysis. Thus, our findings demonstrate that glutamine supplementation in obesity improves 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE286364 | GEO | 2025/10/14

REPOSITORIES: GEO