What's the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health

Abstract

Marrow adipose tissue (MAT) is functionally distinct from both white and brown adipose tissue and can contribute to systemic and skeletal metabolism. MAT formation is a spatially and temporally defined developmental event, suggesting that MAT is an organ that serves important functions and, like other organs, can undergo pathologic change. The well-documented inverse relationship between MAT and bone mineral density has been interpreted to mean that MAT removal is a possible therapeutic target for osteoporosis. However, the bone and metabolic phenotypes of patients with lipodystrophy argues that retention of MAT may actually be beneficial in some circumstances. Furthermore, MAT may exist in two forms, regulated and constitutive, with divergent responses to hematopoietic and nutritional demands. In this review, we discuss the role of MAT in lipodystrophy, bone loss, and metabolism, and highlight our current understanding of this unique adipose tissue depot.

Keywords: diabetes; lipodystrophy; marrow adipose tissue; marrow fat; osteoporosis.

Figure 1

Publications containing the search terms “yellow marrow,” “marrow fat/fatty marrow,” or “marrow adipose tissue” with time. This graph was generated based on a PubMed search for the terms of interest. Given poor indexing of abstracts before 1950, several additional references were added in manually. In addition to general publication trends, this demonstrates a shift in nomenclature from “yellow marrow” to “marrow fat/fatty marrow” in the 1950s and 1960s. Though there was a resurgence in the use of the term “yellow marrow” in the 1980s, its use is declining again in favor of “marrow adipose tissue.”

Figure 2

Histology of MAT, WAT, and BAT. (A) Human marrow adipose tissue, B: bone. (B) Human subcutaneous white adipose tissue from the thigh. (C) Mouse brown adipose tissue. H&E stain, 200× magnification.

Figure 3

Distribution of marrow adipose tissue and changes skeletal adiposity with time. (A) Distribution of marrow adipose tissue (yellow marrow) and hematopoietic or red marrow in an adult skeleton. (B) The percentage of subjects with fatty conversion of the marrow in the phalanges of the 2nd toe at autopsy relative to birth (age 0 weeks). Grade III: some mature adipocytes present, Grade IV: mostly fat with some islands of hematopoiesis, Grade V: complete fatty conversion. (C) Loss of red marrow in the appendicular (femur) and axial skeleton (rib, sternum, and vertebra) with age. Dashed line: approximate age of mature MAT phenotype in the appendicular skeleton.

Figure 4

T1-weighted MRI images of WAT and MAT in CGL. Transverse T1-weighted MRI cross-sections of the limb (top row) and skull at the level of the orbits (bottom row) in patients with CGL as compared to control. In the limb of a normal control a thick layer of subcutaneous adipose tissue (white) is present around a core of muscle (gray). In the center is bone (black) that is filled with marrow adipose tissue (white). Both subcutaneous and marrow adipose tissue are absent in CGL1 and CGL2. In CGL3 and CGL4, subcutaneous fat is lost while marrow fat is maintained. In the cranial section, a layer of mechanical white adipose tissue is present around the skull and behind the orbits. Both mechanical depots are maintained in CGL1, both are lost in CGL2, and the fat behind the orbits but not around the skull is present in CGL3 and CGL4. Images for normal (age 30, female, femur), CGL1 (age 31, female, femur), and CGL2 (age 11, female, femur) from Ref. ; CGL3 (age 19, female, tibia) from Ref. ; and CGL4 (Age 14, male, humerus) from Ref. .

Figure 5

Osteolytic skeletal lesions in CGL and AGL. (A), (B) Multicystic transformation of the distal femur in a 42-year-old Kurdish woman with CGL. The lesion remained relatively unchanged between age 31 and 42 and showed coarse trabeculation of cystic areas filled with high, fluid-like signal intensity on T2-weighted MRI images. (C) Bilateral lesions of the distal humeri, distal radii, proximal and distal ulnae, and phalanges of the hand were noted in a 17-year-old female with CGL that became progressively worse by age 22 and resulted in pathologic fracture of the right humerus at age 23 and the left forearm at age 24. Lesions of the left distal humerus (white arrows) and proximal ulna (black arrows) are shown in panel C. (D) Bilateral unicameral bone cysts of the femoral diaphysis (right femur pictured) in a 13-year-old male with acquired general lipodystrophy. Distal extension noted by the white arrows.

Figure 6

Distribution of marrow adipose tissue in osteoporosis and plasmacytoma. (A) 75-year-old female with osteoporosis and paratrabecular accumulation of marrow adipocytes. (B) Increase in marrow adipocytes in central spaces in a patient with plasmacytoma.

Figure 7

Reconversion of yellow to red marrow in hypertensive heart failure. (A) Control femur from a 61-year-old male. (B) Right femur from a 63-year-old female with hypertensive heart failure. (C) Diagram of marrow content in 10 control female femurs at autopsy (white = yellow marrow, black = red marrow). (D) Diagram of marrow content of 10 femurs from female patients with hypertensive heart failure at autopsy.