Bone marrow rewired: Trained immunity and clonal hematopoiesis in metabolic disease

Diseases associated with obesity and metabolic dysregulation, such as diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD) promote chronic low-grade inflammation, which in turn, may enhance the risk for cardiovascular disease. Emerging evidence in recent years suggests that chronicity of inflammation involves alterations in bone marrow homeostasis. Obesity-related inflammation and metabolic stress, including hyperglycemia or hyperlipidemia, may trigger rewiring of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow, driving production of myeloid cells with heightened inflammatory capacity that in turn fuel and sustain chronic inflammation. This process is akin to trained immunity and may promote an inflammatory memory that links metabolic disorders to their cardiovascular complications. Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by aging-related emergence of somatic mutations in hematopoietic cells that clonally expand and bear higher inflammatory potential. Importantly, a bidirectional link between CHIP and metabolic disorders as well as their cardiovascular sequelae emerges. Here, we review current concepts regarding the links between bone marrow biology and metabolic diseases and associated chronic inflammation.