Model of how obesity promotes the progression of MGUS to MM. Fat depots such as WAT and BMAT secrete proinflammatory cytokines, growth factors, and adipokines that promote MM proliferation and cell growth. Lipids released from adipocytes act not only as fuel for cancer cell growth but also promote the formation of lysolipids that antigenically stimulate plasma cell proliferation. FAs are also transported across membranes by various FA transporters and affect cell signaling to promote MM cell growth. MM cells closely interact with and adhere to BMAds in the BM, which allows MM cell autophagy, trafficking, and proliferation. Within the BM microenvironment, increased adiposity promotes osteoclast differentiation and activity while repressing osteoblast differentiation and activity. Furthermore, proinflammatory cytokines also promote osteoclast activity, which contributes to bone fragility in patients with MM and promotes a prooncogenic niche for MM cell expansion. Dec, decrease; Inc, increase.