What is Bone Marrow Adipose Tissue (BMAT)?
Once considered merely an inert packing material to fill the spaces within bones, bone marrow adipose tissue (BMAT), or bone fat, is now recognized as a complex and dynamic organ. Found within the bone cavities, BMAT is unique compared to other fat deposits like subcutaneous or visceral fat due to its distinct molecular and functional characteristics. Rather than being a simple storage site, BMAT is an active regulator of bone metabolism, blood cell production (hematopoiesis), and systemic energy balance. Its adipocytes, or fat cells, secrete a range of hormones and factors that affect the body on both a local and systemic level.
The Two Types of Bone Marrow Fat
BMAT is not a uniform tissue; instead, it is composed of two distinct populations, which differ in location, composition, and responsiveness to metabolic signals. These two types are:
- Constitutive Marrow Adipose Tissue (cMAT): This type develops early in life and is primarily found in the distal parts of the skeleton, such as the hands and feet. cMAT is generally resistant to being used for energy during caloric restriction or fasting and contains a higher proportion of unsaturated fatty acids. Its primary function appears to be local metabolic and structural support, and it is less involved in regulating hematopoiesis.
- Regulated Marrow Adipose Tissue (rMAT): Found mainly in the vertebrae, pelvis, and proximal long bones (like the femur), rMAT develops gradually throughout life and is more metabolically active. Unlike cMAT, rMAT can be mobilized for energy in response to stress or starvation. It is also more closely involved in regulating the hematopoietic microenvironment, where blood cells are produced.
Key Functions of Bone Fat
The recognition of BMAT as a functional organ has highlighted its vital roles in human health. Its key functions include:
- Energy Storage: As with other adipose tissues, BMAT is a significant energy reservoir, storing lipids that can be mobilized to fuel neighboring cells during periods of high demand. This can occur during intense exercise or periods of caloric restriction, where fatty acids are released into the bloodstream.
- Endocrine Function: BMAT acts as an endocrine organ, secreting various signaling molecules like hormones (leptin and adiponectin), cytokines, and growth factors. Leptin, for example, is a hormone that regulates appetite and has an anabolic effect on bone formation.
- Hematopoiesis Regulation: BMAT is a key part of the hematopoietic niche, the microenvironment where blood-forming stem cells (HSCs) reside. It provides metabolic and mechanical support for HSCs, influencing their proliferation, differentiation, and survival through the secretion of factors like SCF (stem cell factor).
- Bone Metabolism: There is a competitive balance between the differentiation of mesenchymal stem cells (MSC) into either osteoblasts (bone-forming cells) or adipocytes (fat cells). Factors that promote adipogenesis in the marrow, such as age-related changes or inflammation, can suppress osteoblast formation, leading to a net loss of bone mass.
How Bone Fat Changes with Age
One of the most notable changes in BMAT is its increase with age. At birth, the majority of the bone marrow is red and hematopoietically active. This gradually converts to yellow, fatty marrow in a process that begins in the extremities and moves toward the central skeleton. By around age 25, red marrow is mostly confined to the axial skeleton and proximal long bones.
With further aging, this yellowing continues, and BMAT volume increases while bone mineral density and hematopoietic activity decline. This is partly due to mesenchymal stem cells shifting their differentiation from osteoblasts toward adipocytes. This age-related increase in BMAT is associated with a higher risk of osteoporosis and fragility fractures in the elderly.
The Connection Between Bone Fat and Disease
Research has uncovered strong links between variations in bone fat and a wide range of diseases. Scientists have found evidence that excess BMAT may not just be a symptom but may actively contribute to crippling conditions. An AI analysis of MRI scans linked bone marrow adiposity to 47 different diseases.
Bone Fat and Osteoporosis
High levels of BMAT are consistently associated with lower bone mineral density (BMD) and an increased risk of osteoporosis. The inverse relationship exists because osteoblasts and adipocytes originate from the same precursor stem cells. When conditions favor adipogenesis (fat cell formation) over osteogenesis (bone formation), bone mass is compromised. Factors contributing to this imbalance include aging, estrogen deficiency (as seen in postmenopausal women), and chronic inflammation. A lower unsaturation index (UI) in BMAT, indicating a higher saturated fatty acid content, is also linked to poorer skeletal health.
Bone Fat and Metabolic Diseases
BMAT is a metabolically active organ with connections to systemic energy metabolism and conditions like diabetes and obesity.
- Diabetes: Studies show that increased BMAT is present in both type 1 and type 2 diabetes, and high glucose levels can promote adipogenic differentiation over osteogenic differentiation. The fat can serve as a lipid source for tumor cells in bone metastasis, particularly in breast and prostate cancers.
- Obesity: While obesity is often associated with higher overall fat, it does not always correlate directly with BMAT levels. However, weight loss via methods like bariatric surgery has been shown to reduce BMAT, along with total body fat.
Bone Fat in Anorexia Nervosa
In a unique paradox, individuals with anorexia nervosa exhibit significantly increased BMAT despite a severe lack of total body fat. This phenomenon, accompanied by reduced bone mineral density, suggests that BMAT regulation is distinct from other fat depots and can be driven by hormonal and metabolic signals related to malnutrition.
Measuring Bone Fat: The Role of MRI
In vivo measurement of BMAT has revolutionized research into its function and links to disease. Magnetic Resonance Imaging (MRI) and Proton Magnetic Resonance Spectroscopy (1H MRS) are key techniques used.
Comparison of Techniques for BMAT Measurement
| Feature | Magnetic Resonance Imaging (MRI) | Proton Magnetic Resonance Spectroscopy (1H MRS) |
|---|---|---|
| Principle | Distinguishes fat from hematopoietic marrow based on signal differences on T1-weighted sequences. | Quantifies BMAT as a percentage of water, providing a fat fraction value. |
| Strengths | Excellent anatomical detail; visualizes spatial distribution of red and yellow marrow. | High reproducibility and superior quantification of fat content within a specific volume. |
| Limitations | Doesn't provide quantitative data on fat fraction unless combined with other methods. | Limited by the heterogeneous distribution of fat in bones if only a small area is sampled. |
| Additional Data | Can be used with whole-body protocols to overcome non-uniform distribution. | Can also analyze lipid composition (e.g., saturation levels), which may correlate with bone health. |
Future Directions in Bone Fat Research
As scientists continue to understand BMAT's complex roles, new therapeutic avenues are emerging. The ability of BMAT to secrete regulatory factors and influence stem cell differentiation makes it a potential target for treating various conditions. For instance, drugs that can modulate BMAT activity or prevent its pathological expansion could help prevent bone loss in osteoporosis or aid hematopoietic recovery after therapies.
One study, for example, explores how a hormone called adipsin, found in bone fat, may control bone and fat production. Compounds that block this hormone are being investigated as potential treatments for age-related vision loss but could potentially be repurposed to increase bone mass in older people with osteoporosis. For more information on ongoing research in this area, see this Frontiers review.
Conclusion: The Active Role of Bone Fat
Bone fat is no longer viewed as a static, passive component of the skeletal system. Research has fundamentally changed our understanding of what bone fat means, revealing it to be a dynamic, metabolically active organ. Its functions extend far beyond simple energy storage, playing crucial roles in endocrine signaling, hematopoiesis, and bone remodeling. This active involvement means that disruptions in BMAT are linked to a host of diseases, including osteoporosis, diabetes, and certain cancers. As diagnostic and imaging technologies advance, leveraging our knowledge of BMAT may offer new strategies for disease prediction and developing targeted therapies to address these complex health issues.
