Abstract
The goal of this review is to discuss the role of insulin signaling in bone marrow adipocyte formation, metabolic function, and its contribution to cellular senescence in relation to metabolic bone diseases.
Insulin signaling is an evolutionally conserved signaling pathway that plays a critical role in the regulation of metabolism and longevity. Bone is an insulin-responsive organ that plays a role in whole body energy metabolism. Metabolic disturbances associated with obesity and type 2 diabetes increase a risk of fragility fractures along with increased bone marrow adiposity. In obesity, there is impaired insulin signaling in peripheral tissues leading to insulin resistance. However, insulin signaling is maintained in bone marrow microenvironment leading to hypermetabolic state of bone marrow stromal (skeletal) stem cells associated with accelerated senescence and accumulation of bone marrow adipocytes in obesity. This review summarizes current findings on insulin signaling in bone marrow adipocytes and bone marrow stromal (skeletal) stem cells and its importance for bone and fat metabolism. Moreover, it points out to the existence of differences between bone marrow and peripheral fat metabolism which may be relevant for developing therapeutic strategies for treatment of metabolic bone diseases.