Increased bone marrow adiposity is associated with bone fragility in metabolic diseases such as obesity. Bone marrow adipose tissue (BMAT) originates from bone marrow mesenchymal stem cells (BMSCs), which can differentiate into adipocytes,osteoblasts or chondrocytes. With obesity, the function of key building blocks, bone marrow stromal cells (BMSCs) changes towards higher accumulation of BMAT, which is affected by diet and sex dimorphism. Our recent findings reported that BMAT acts as a unique fat depot that does not develop insulin resistance in obesity compared to peripheral adipose. Our research is focused on identifying metabolic pathways contributing to senescent phenotype in BMSCs and modulate their function to improve bone and fat metabolism in animal models of metabolic diseases with respect to sex dimorphism.