Obesity and type 2 diabetes accompanied by increased accumulation of bone marrow adipose tissue (BMAT) affect bone homeostasis. Using anti-diabetic drugs such as thiazolidinediones (TZDs) has a different effect on bone and fat physiology, pointing out a dual role of common factors present in periphery and bone marrow. Insulin signaling, lipid handling, oxidoreductase activity are nutrient-sensing pathways, which are affected by metabolic disturbances and play a critical role in the regulation of glucose metabolism and bone homeostasis. Here I will review our current findings on metabolic changes in BMAT phenotype and its effect on bone marrow microenvironment and stem cell properties in obesity. Also, I will present our recent data with different interventional approaches in animal models of obesity and its effect on BMAT and bone phenotype.