Marrow adipose tissue

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Marrow adipose tissue_table_infobox_0

Marrow adipose tissueMarrow adipose tissue_header_cell_0_0_0

Marrow adipose tissue (MAT), also known as bone marrow adipose tissue (BMAT), is a type of fat deposit in bone marrow. Marrow adipose tissue_sentence_0

It increases in states of low bone density -osteoporosis, anorexia nervosa/ caloric restriction, skeletal unweighting such as that which occurs in space travel, anti-diabetes therapies. Marrow adipose tissue_sentence_1

Origin Marrow adipose tissue_section_0

The marrow adipocytes originate from mesenchymal stem cell (MSC) progenitors that also give rise to osteoblasts, among other cell types. Marrow adipose tissue_sentence_2

Thus, it is thought that MAT results from preferential MSC differentiation into the adipocyte, rather than osteoblast, lineage in the setting of osteoporosis. Marrow adipose tissue_sentence_3

Since MAT is increased in the setting of obesity and is suppressed by endurance exercise, or vibration, it is likely that MAT physiology, in the setting of mechanical input/exercise, approximates that of white adipose tissue (WAT). Marrow adipose tissue_sentence_4

Exercise regulation of marrow adipose tissue Marrow adipose tissue_section_1

The first study to demonstrate exercise regulation of MAT in rodents was published in 2014; Now, exercise regulation of MAT has been confirmed in a humansl adding clinical importance. Marrow adipose tissue_sentence_5

Several studies demonstrated exercise reduction of MAT which occurs along with an increase in bone quantity. Marrow adipose tissue_sentence_6

Since exercise increases bone quantity, reduces MAT and increases expression of markers of fatty acid oxidation in bone, MAT is thought to be providing needed fuel for exercise-induced bone formation or anabolism. Marrow adipose tissue_sentence_7

One notable exception occurs in the setting of caloric restriction: exercise suppression of MAT does not yield an increase in bone formation and even appears to cause bone loss. Marrow adipose tissue_sentence_8

Indeed, energy availability appears to be a factor in the ability of exercise to regulate MAT. Marrow adipose tissue_sentence_9

Relationships to other types of fat Marrow adipose tissue_section_2

MAT has qualities of both white and brown fat. Marrow adipose tissue_sentence_10

Subcutaneous white fat contain excess energy, indicating a clear evolutionary advantage during times of scarcity. Marrow adipose tissue_sentence_11

WAT is also the source of adipokines and inflammatory markers which have both positive (e.g., adiponectin) and negative effects on metabolic and cardiovascular endpoints. Marrow adipose tissue_sentence_12

Visceral abdominal fat (VAT) is a distinct type of WAT that is "proportionally associated with negative metabolic and cardiovascular morbidity", regenerates cortisol, and recently has been tied to decreased bone formation Both types of WAT substantially differ from brown adipose tissue (BAT) as by a group of proteins that help BAT’s thermogenic role. Marrow adipose tissue_sentence_13

MAT, by its "specific marrow location, and its adipocyte origin from at least LepR+ marrow MSC is separated from non-bone fat storage by larger expression of bone transcription factors", and likely indicates a different fat phenotype. Marrow adipose tissue_sentence_14

Recently, MAT was noted to "produce a greater proportion of adiponectin - an adipokine associated with improved metabolism - than WAT", suggesting an endocrine function for this depot, akin, but different, from that of WAT. Marrow adipose tissue_sentence_15

Impact on bone health Marrow adipose tissue_section_3

MAT increases in states of bone fragility. Marrow adipose tissue_sentence_16

MAT is thought to result from preferential MSC differentiation into an adipocyte, rather than osteoblast lineage in osteoporosis based on the inverse relationship between bone and MAT in bone-fragile osteoporotic states. Marrow adipose tissue_sentence_17

An increase in MAT is noted in osteoporosis clinical studies measured by MR Spectroscopy. Marrow adipose tissue_sentence_18

Estrogen therapy in postmenopausal osteoporosis reduces MAT. Marrow adipose tissue_sentence_19

Antiresorptive therapies like risedronate or zoledronate also decrease MAT while increasing bone density, supporting an inverse relationship between bone quantity and MAT. Marrow adipose tissue_sentence_20

During aging, bone quantity declines and fat redistributes from subcutaneous to sites such as bone marrow, muscle, and liver. Marrow adipose tissue_sentence_21

Aging is associated with lower osteogenic and greater adipogenic biasing of MSC. Marrow adipose tissue_sentence_22

This aging-related biasing of MSC away from osteoblast lineage may represent higher basal PPARγ expression or decreased Wnt10b. Marrow adipose tissue_sentence_23

Thus, bone fragility, osteoporosis, and osteoporotic fractures are thought to be linked to mechanisms which promote MAT accumulation. Marrow adipose tissue_sentence_24

Marrow adipose tissue_unordered_list_0

  • Histologic sections demonstrating Marrow AdipocytesMarrow adipose tissue_item_0_0
  • Marrow adipose tissue_item_0_1
  • Marrow adipose tissue_item_0_2

Maintenance of hematopoietic stem cells Marrow adipose tissue_section_4

Bone marrow adipocytes secrete factors that promote HSC renewal in most bones. Marrow adipose tissue_sentence_25

Hematopoietic cells (also known as blood cells) reside in the bone marrow along with marrow adipocytes. Marrow adipose tissue_sentence_26

These hematopoietic cells are derived from hematopoietic stem cells (HSC) which give rise to diverse cells: cells of the blood, immune system, as well as cells that break down bone (osteoclasts). Marrow adipose tissue_sentence_27

HSC renewal occurs in the marrow stem cell niche, a microenvironment that contains cells and secreted factors that promote appropriate renewal and differentiation of HSC. Marrow adipose tissue_sentence_28

The study of the stem cell niche is relevant to the field of oncology in order to improve therapy for multiple hematologic cancers. Marrow adipose tissue_sentence_29

As such cancers are often treated with bone marrow transplantation, there is interest in improving the renewal of HSC. Marrow adipose tissue_sentence_30

Measurement Marrow adipose tissue_section_5

In order to understand the physiology of MAT, various analytic methods have been applied. Marrow adipose tissue_sentence_31

Marrow adipocytes are difficult to isolate and quantify because they are interspersed with bony and hematopoietic elements. Marrow adipose tissue_sentence_32

Until recently, qualitative measurements of MAT have relied on bone histology, which is subject to site selection bias and cannot adequately quantify the volume of fat in the marrow. Marrow adipose tissue_sentence_33

Nevertheless, histological techniques and fixation make possible visualization of MAT, quantification of adipocyte size, and MAT’s association with the surrounding endosteum, milieu of cells, and secreted factors. Marrow adipose tissue_sentence_34

Recent advances in cell surface and intracellular marker identification and single-cell analyses led to greater resolution and high-throughput ex-vivo quantification. Marrow adipose tissue_sentence_35

Flow cytometric quantification can be used to purify adipocytes from the stromal vascular fraction of most fat depots. Marrow adipose tissue_sentence_36

Early research with such machinery cited adipocytes as too large and fragile for cytometer-based purification, rendering them susceptible to lysis; however, recent advances have been made to mitigate this; nevertheless, this methodology continues to pose technical challenges and is inaccessible to much of the research community. Marrow adipose tissue_sentence_37

To improve quantification of MAT, novel imaging techniques have been developed as a means to visualize and quantify MAT. Marrow adipose tissue_sentence_38

Although proton magnetic resonance spectroscopy (1H-MRS) has been used with success to quantify vertebral MAT in humans, it is difficult to employ in laboratory animals. Marrow adipose tissue_sentence_39

Magnetic resonance imaging (MRI) provides MAT assessment in the vertebral skeleton in conjunction with μCT-based marrow density measurements. Marrow adipose tissue_sentence_40

A volumetric method to identify, quantify, and localize MAT in rodent bone has been recently developed, requiring osmium staining of bones and μCT imaging, followed by advanced image analysis of osmium-bound lipid volume (in mm) relative to bone volume. Marrow adipose tissue_sentence_41

This technique provides reproducible quantification and visualization of MAT, enabling the ability to consistently quantify changes in MAT with diet, exercise, and agents that constrain precursor lineage allocation. Marrow adipose tissue_sentence_42

Although the osmium method is quantitatively precise, osmium is toxic and cannot be compared across batched experiments. Marrow adipose tissue_sentence_43

Recently, researchers developed and validated a 9.4T MRI scanner technique that allows localization and volumetric (3D) quantification that can be compared across experiments, as in. Marrow adipose tissue_sentence_44

Marrow adipose tissue_unordered_list_1

  • Methods for Quantification of Marrow Adipose Tissue (MAT)Marrow adipose tissue_item_1_3
  • Marrow adipose tissue_item_1_4
  • Marrow adipose tissue_item_1_5

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: adipose tissue.