Figure 1.

Hypothetical working model for obesity-induced niche changes in human BM. HFD decreases CXCL12 expression in the BM, induces HSC activation and differentiation resulting in a shift from self-renewing HSCs toward mature progenitors with a myeloid bias. Obesity increases circulating levels of proinflammatory cytokines and ROS. MSCs of obese BM are senescent and exhausted possibly mediated by the increased ROS levels. Obesity/HFD suppress osteogenic and induce adipogenic differentiation of MSCs leading to an expansion of BMAT. Exercise counteracts the systemic effect of obesity by improving body composition and decreasing the systemic inflammation. Furthermore, exercise may improve the obesity-induced niche changes by decreasing the amount of BMAT and increasing osteoblast differentiation. Furthermore, exercise may balance the quiescence versus active state of HSCs. BM = bone marrow; BMAT = bone marrow adipose tissue; CXCL12 = C-X-C motif ligand 12; ECs = endothelial cells; HFD = high-fat diet; HSC = hematopoietic stem cell; MSC = mesenchymal stromal cell; OBs = osteoblasts; OCs = osteoclasts; ROS = reactive oxygen species. Created with BioRender.