Schematic (adapted from Ref. 49) depicts the bone marrow cellular niche (right) and muscle cellular niche (left). The bone marrow is a dynamic heterogeneous environment and home to mesenchymal and hematopoietic stem cells. Mesenchymal stem cells regulate bone and fat systems in the marrow and support the hematopoietic niche. Hematopoietic stem cells regulate blood and immune cells, which can be compromised by obesity. The skeletal muscle microenvironment comprises multinucleated myofibers and stem cells, including satellite cells, mesenchymal progenitors, and fibro/adipogenic progenitors. Obesity results in increased intramyocellular lipid accumulation within myofibers and increased local adipocytes, likely through mesenchymal or fibro/adipogenic progenitor differentiation. This change is paralleled in the marrow, where increased marrow adipose tissue is characteristic of conditions with excess adiposity. Maintaining healthy levels of fat in bone and muscle may be achieved through mechanical stimulation intervention and biasing stem cell differentiation away from adipogenesis.