The Effect of Nutritional Transition on the Differentiation of Bone Marrow Stem Cells and the Therapeutic Effect of GLP-1

Background: Catch up growth is associated with glucose and lipid metabolism disorders, that can lead to osteoporosis and related fractures. Glucagon-like peptide-1 receptor agonists, such as liraglutide, exert an anabolic effect on bone in insulin resistant mice, but the mechanism for the action remains unclear. We established an animal model of catch-up growth to explore the actions of GLP-1 on bone mass and structure. Methods: 30 male C57BL/6 mice were randomly divided into the normal diet (ND, n=10), the catch-up growth model (RH, n=10) and the catch-up growth model +GLP-1 (RH+GLP-1, n=10) groups. Liraglutide was subcutaneously administered (200ug/kg, twice a day, for four weeks). After killing, tibia and fibula were removed for bone histomorphometry, bilateral femoral bone marrow mesenchymal stem cells were collected to evaluate their differentiation ability. Results: GLP-1 administration decreased weight of visceral fat tissue, body weight, ratio between them, and blood lipids of the RH group. GLP-1 decreased triglyceride levels, and fatty acids in the liver, visceral fat tissue, subcutaneous fat tissue and skeletal muscle tissue. Compared to the ND group, GLP-1 secretion decreased in the RH group, but noticeably increased after GLP-1 administration. The areas under curves of intraperitoneal glucose tolerance test and insulin tolerance test and HOMA-IR in RH+GLP-1 group significantly declined. GLP-1 reversed deteriorated tibial and fibular bone structure in RH mice and induced osteoblastic differentiation. Conclusion: Decreased ability of osteoblastic/osteogenesis differentiation of MSCs in RH mice led to impaired bone formation and GLP-1 intervention reversed the damage and enhanced insulin sensitivity. Disclosure W. Xia: None. L. Chen: None. Q. Zhang: None.