Bone Marrow Adipose Tissue Dynamics and Metabolic Interactions

Bone marrow adipose tissue (BMAT) represents a specialised fat depot within the skeletal microenvironment that interweaves local support of haematopoiesis and bone remodelling with broader metabolic regulation. Unlike subcutaneous or visceral fat, marrow adipocytes arise from mesenchymal progenitors amid trabecular bone and secrete adipokines, cytokines and free fatty acids that modulate osteoblast and osteoclast activity. BMAT expands during ageing, menopause, obesity and caloric restriction, often in parallel with bone loss or haematopoietic stress. Its cellular and molecular dynamics are governed by an interplay of transcriptional regulators, nutrient sensors and endocrine signals, leading to depot-specific heterogeneity in adipocyte size, lipid composition and responsiveness to insulin or cold. Emerging imaging and ex vivo models have unveiled BMAT’s capacity to buffer systemic glucose, influence vascular niches and sculpt tumour microenvironments. Together, these features position BMAT as both a regulator of skeletal integrity and a contributor to whole-body metabolic homeostasis.

Research from Nature Portfolio

Recent studies have revealed that inhibiting the nuclear receptor ESRRA in bone marrow adipocytes preserves osteogenesis and type H vessel formation under conditions of oestrogen deficiency or obesity by shifting the balance of leptin and osteopontin secretion, thereby promoting stromal stem cell differentiation towards osteoblasts. In vivo blockade of ESRRA mitigates marrow adiposity and protects against bone loss. Parallel transcriptomic and in vivo imaging investigations have characterised BMAT as distinct from white and brown fat, showing reduced insulin- and cold-stimulated glucose uptake yet elevated basal glucose consumption in human axial bone. These findings underscore BMAT’s unique metabolic fingerprint and its potential to influence systemic glucose homeostasis. Earlier foundational work delineated two anatomically and functionally discrete MAT subpopulations: proximal “regulated” MAT interspersed with active haematopoiesis and responsive to systemic cues, and distal “constitutive” MAT composed of larger, developmentally earlier adipocytes that persist under physiological stress. Recognising these subtypes has refined our understanding of marrow fat’s heterogeneous roles in bone biology and energy metabolism.

Bone Marrow Adipose Tissue Dynamics and Metabolic Interactions publication trend

The graph below shows the total number of articles in bone marrow adipose tissue dynamics and metabolic interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Bone marrow adipose tissue (BMAT): A unique adipose depot within bone marrow comprising adipocytes that interact with bone and haematopoietic cells.

Marrow adipocytes (BMAds): Fat cells derived from mesenchymal progenitors in the bone marrow stroma.

Regulated MAT (rMAT): Proximal marrow adipose tissue interspersed with active haematopoiesis and responsive to systemic metabolic cues.

Constitutive MAT (cMAT): Distal marrow adipose tissue comprising larger adipocytes that develop early and remain stable under systemic stress.

ESRRA (Estrogen-Related Receptor α): A nuclear receptor that regulates adipocyte transcriptional responses to metabolic stress.

RANKL (Receptor Activator of NF-κB Ligand): A cytokine essential for osteoclast differentiation and bone resorption.

Mesenchymal stromal cells (MSCs): Multipotent progenitors in the bone marrow capable of differentiating into osteoblasts, adipocytes and other stromal lineages.

Lipolysis: The enzymatic breakdown of stored triglycerides into free fatty acids and glycerol.

Paracrine signalling: Cell-to-cell communication via the secretion of signalling molecules that act locally.

References

1. Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow. Nature Communications (2024).
2. Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. Nature Communications (2020).
3. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nature Communications (2015).
4. GelMA and Biomimetic Culture Allow the Engineering of Mineralized, Adipose, and Tumor Tissue Human Microenvironments for the Study of Advanced Prostate Cancer In Vitro and In Vivo. Advanced Healthcare Materials (2023).
5. RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss. EMBO Reports (2021).
6. Human Bone Marrow Is Comprised of Adipocytes with Specific Lipid Metabolism. Cell Reports (2020).