Metabolic Coupling Between Bone Marrow Adipose Tissue and Hematopoiesis

Abstract

An important physiological function of MAT may be to provide an expandable/contractible fat depot, which is critical for minimization of energy requirements for sustaining optimal hematopoiesis. Because the energy requirements for storing fat are negligible compared to those required to maintain hematopoiesis, even small reductions in hematopoietic tissue volume to match a reduced requirement for hematopoiesis could represent an important reduction in energy cost. Such a physiological function would require tight coupling between hematopoietic stem cells and MSCs to regulate the balance between MAT and hematopoiesis. Kit-ligand, an important regulator of proliferation, differentiation, and survival of hematopoietic cells, may function as a prototypic factor coupling MAT and hematopoiesis. Crosstalk between hematopoietic and mesenchymal cells in the bone marrow may contribute to establishing the balance between MAT levels and hematopoiesis.

Voluntary Chronic Heavy Alcohol Consumption in Male Rhesus Macaques Suppresses Cancellous Bone Formation and Increases Bone Marrow Adiposity

“…Based on this model, metabolic coupling between mesenchymal and hematopoietic cells in bone marrow regulates MAT levels. Thus, the well‐established inhibitory effects of chronic alcohol consumption on hematopoiesis may be responsible for increased MAT here and in rodent models (Heermans, ; Siggins et al., ; Turner et al., ).…”

“…Osteoblasts and bone marrow adipocytes originate from the same bone marrow mesenchymal stem cells, and in vitro studies suggest that, at high concentrations, alcohol decreases osteoblast number by modulating the differentiation program of stem cells to form adipocytes at the expense of osteoblasts (Chen et al., ; Wezeman and Gong, ). However, there is also evidence that osteoblasts and marrow adipocytes are regulated independently (Turner et al., ). Specifically, we have shown that neither pathological increases in marrow adiposity following hypophysectomy in rats (Menagh et al., ) nor absence of marrow adiposity in mice with loss‐of‐function mutations in c‐kit signaling (Iwaniec and Turner, ; Keune et al., ) influence the skeletal response to bone anabolic or catabolic factors.…”

“…There has been a recent upsurge in interest in the role of marrow adipose tissue (MAT) in health and disease (Li et al., ; Veldhuis‐Vlug and Rosen, ), with most research focusing on bone marrow adipocytes as likely negative modulators of bone remodeling balance (Turner et al., ; Veldhuis‐Vlug and Rosen, ). However, research using genetic models has led to the proposal that changes in marrow adiposity reflect physiological adaptation.…”

Effects of Propranolol on Bone, White Adipose Tissue, and Bone Marrow Adipose Tissue in Mice Housed at Room Temperature or Thermoneutral Temperature

“…The quantity of bMAT in distal femur metaphysis is context-dependent and, as recently reviewed (35), influenced by numerous factors, including skeletal site, age, food availability, and housing temperature. Increased bMAT occurs with extremes in energy availability; obesity and rapid weight loss each result in increased bMAT.…”

Three‐dimensional intravital imaging in bone research

“…It should be noted that other cell types in bone also play a role in bone biology, such as neuron cells. More recently, adipocytes in the BM space have been demonstrated to exert impacts on osteogenesis , hematopoiesis and tumor survival . However, IVI has not been employed for investigation of fluorescence labeled neuron cells and adipocytes in bone.…”