Bone-related disorders such as osteoporosis affect millions of people worldwide, placing a heavy burden on patients, their families, and healthcare systems alike. In many of these conditions, decreased bone formation is closely associated with increased bone marrow adiposity. Interestingly, bone composition and function are significantly affected by changes in diet and metabolic disorders such as diabetes and obesity. However, the role of metabolism in regulating bone mesenchymal lineage decisions and cell function in the bone marrow microenvironment is at the early stages of understanding. In this project, I used advanced mouse genetics and high-resolution imaging techniques to investigate the role of metabolism in the differentiation and function of mesenchymal cell types in bone, with a particular focus on the adipocyte lineage. Using single-cell RNA sequencing techniques, I characterised the diverse bone marrow adipocyte lineage cells in the mouse bone marrow. A previously unknown cell type, characterised by expression of Gata2, Gas5, Cd34, and Kit, was found to be dependent on the serine synthesis pathway via Phgdh, and was implicated in diet-induced adipogenesis. Cell type specific deletions of Cpt1a and Pfkfb3 demonstrated sex differences in fatty acid and glucose metabolism of bone marrow adipocytes, indicating a particularly important role in females. Similarly, metabolic alterations in smooth muscle cells, chondrocytes, and osteoblasts confirmed the importance of glycolysis, fatty acid oxidation, and glutamine metabolism for the proliferation and function of these distinct mesenchymal cell types. Overall, the findings of this project suggest that targeting metabolic pathways, specifically fatty acid, glutamine, and serine metabolism, may be promising strategies to reduce bone marrow adiposity and promote bone formation, particularly for women, and could inform the management of bone health in metabolic disorders in the future.