Full Length ArticleDevelopment, regulation, metabolism and function of bone marrow adipose tissues
Introduction
Adipocytes are found in white (WAT) and brown adipose tissues, as well as in bone marrow adipose tissue (BMAT) and other more minor depots [[1], [2], [3], [4]]. Although adipocytes were identified in human bone marrow more than a century ago, the origin, development, function and interaction of these adipocytes with other cells within bone marrow were largely unstudied until recently [3, 5]. BMAT develops in a distinct pattern throughout the skeleton and is dynamically regulated by a variety of physiological and pathological conditions. Herein we delineate the differences between bone marrow adipocytes (BMAs) within red and yellow marrow, which we have defined as regulated (r) and constitutive (c) BMAT, with rBMAT showing more dynamic responses to a variety of conditions. We also review the development and regulation of BMAT in human and rodents under physiological and pathological conditions, explore the local functions of BMAT related to osteogenesis and hematopoiesis, and compare the secretome and lipid composition of BMAT with that of more well-characterized white depots.
Section snippets
Continual development of BMAT over the human lifespan
BMAT resides within the bone cavity together with hematopoietic cells, trabecular bone, nerve fibers, blood vessels and sinusoidal capillaries [6]. At birth, bone marrow is mainly composed of hematopoietic cells, and is thus known as red marrow due to the color from erythroid cells. The number of adipocytes within bone marrow increases dramatically during postnatal growth, causing the bone color to change from red to yellow. In general, expansion of BMAT occurs in a centripetal pattern,
Functional interactions between BMA and other cells within the bone marrow niche
BMAT is undoubtedly an important component of the bone and hematopoietic niches; however, the specific relationships between BMAs and osteoblasts/osteoclasts, and hematopoietic cells have not yet been well-defined in a mechanistic manner. Bone, hematopoietic cells, and BMAs are contained within a closed system, and thus expansion of one of these populations is often at the expense of one or both of the others. Although this reciprocal relationship undoubtedly holds true at the extremes,
Secretion of a subset of adipokines by BMAT
There is no evidence from gene profiling or expression studies that any of the myriad adipokines secreted from WAT are not also expressed by BMAT [74, 75]. However, differences in relative expression and/or secretion of proteins from WAT and BMAT exist, and likely reflect the distinctive functions and properties of each depot. For example, leptin is well-known to be expressed in proportion to adipocyte size [76]. Thus, whilst the mRNA for leptin is reported to be reduced (or unchanged) in BMAs [
Unsaturated lipid composition of cBMAT
The distinct lipid composition of BMAs isolated from red and yellow marrow was first identified in rabbits by Tavassoli et al. in 1977 [80]. He reported that āshifts from myristic and palmitic acids (in red marrow) to their respective monounsaturated derivatives myristoleic and palmitoleic acids (in yellow marrow) were found.ā These findings generally hold true from humans to rodents [21]. Humans have an increased unsaturation index in bone marrow of distal tibia compared to hip, and lipid
Summary and future directions
It has become clear that BMAT is distinct from other well-characterized adipose depots, such as WAT and brown adipose tissue. In addition to its unique location, BMAT also differs with regards to origin, development, site-specific regulation, cellular character, and function. Although inverse relationships are generally observed between BMAT, bone mass and hematopoietic cellularity within the closed environment of bone, recent mechanistic work sheds light not only on antagonistic interactions,
Funding sources
This work was supported by funds from the NIH to OAM (R24 DK092759; RO1 DK62876), DPB (T32 GM007863; T32 HD007505) and EL (R00 DE024178), and from the American Diabetes Association (1-18-PDF-087) to ZL.
References (82)
- et al.
Adipocyte lineages: tracing back the origins of fat
Biochim. Biophys. Acta
(2014) - et al.
Marrow adipose tissue: trimming the fat
Trends Endocrinol. Metab.
(2016) - et al.
Bone marrow adipose tissue: formation, function and regulation
Curr. Opin. Pharmacol.
(2016) - et al.
Structural and functional imaging of normal bone marrow and evaluation of its age-related changes
Semin. Nucl. Med.
(2007) - et al.
A 3-year longitudinal study on body composition changes in the elderly: role of physical exercise
Clin. Nutr.
(2006) - et al.
Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia
Bone
(2013) - et al.
Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy
Bone
(2016) - et al.
Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction
Cell Metab.
(2014) - et al.
The bone-fat interface: basic and clinical implications of marrow adiposity
Lancet Diabetes Endocrinol.
(2015) - et al.
Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling
Cell Metab.
(2016)
Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma
J. Biol. Chem.
Parathyroid hormone directs bone marrow mesenchymal cell fate
Cell Metab.
Bone marrow adipocytes support dexamethasone-induced osteoclast differentiation
Biochem. Biophys. Res. Commun.
Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage
Bone
Age-related marrow adipogenesis is linked to increased expression of RANKL
J. Biol. Chem.
Red-yellow marrow conversion: its effect on the location of some solitary bone lesions
Skelet. Radiol.
SnapShot: niche determines adipocyte character I
Cell Metab.
Bone marrow imaging
Radiology
Marrow fat and boneānew perspectives
J. Clin. Endocrinol. Metab.
Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis
Biogerontology
One- and two-year change in body composition as measured by DXA in a population-based cohort of older men and women
J. Appl. Physiol.
Normal bone marrow in the sacrum of young adults: differences between the sexes seen on chemical-shift MR imaging
AJR Am. J. Roentgenol.
Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0Ā Tesla
J. Magn. Reson. Imaging
Age- and sex-specific differences in the 1H-spectrum of vertebral bone marrow
J. Magn. Reson. Imaging
3Ā Tesla (1) H MR spectroscopy of hip bone marrow in a healthy population, assessment of normal fat content values and influence of age and sex
J. Magn. Reson. Imaging
Bone marrow fat content in the elderly: a reversal of sex difference seen in younger subjects
J. Magn. Reson. Imaging
Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women
Osteoporos. Int.
Marrow adipose tissue: skeletal location, sexual dimorphism, and response to sex steroid deficiency
Front. Endocrinol.
Fatty involution of bone marrow in rabbits
Acta Anat. (Basel)
Marrow adipose cells. Histochemical identification of labile and stable components
Arch. Pathol. Lab. Med.
Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues
Nat. Commun.
Morbid obesity attenuates the skeletal abnormalities associated with leptin deficiency in mice
J. Endocrinol.
Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment
Nature
Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats
Endocrinology
Effects of basic fibroblast growth factor and a prostaglandin E2 receptor subtype 4 agonist on osteoblastogenesis and adipogenesis in aged ovariectomized rats
J. Bone Miner. Res.
Ovariectomy-associated changes in bone mineral density and bone marrow haematopoiesis in rats
Int. J. Exp. Pathol.
Expansion of bone marrow adipose tissue during caloric restriction is associated with increased circulating glucocorticoids and not with hypoleptinemia
Endocrinology
Analysis of ovariectomy and estrogen effects on body composition in rats by X-ray and magnetic resonance imaging techniques
J. Bone Miner. Res.
Bone marrow adipocytes resist lipolysis and remodeling in response to <beta>-adrenergic stimulation
Bone
Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice
J. Bone Miner. Res.
Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice
J. Bone Miner. Res.
Cited by (92)
Adipose tissue at single-cell resolution
2023, Cell MetabolismObesity, bone marrow adiposity, and leukemia: Time to act
2024, Obesity Reviews