Elsevier

Bone

Volume 110, May 2018, Pages 134-140
Bone

Full Length Article
Development, regulation, metabolism and function of bone marrow adipose tissues

https://doi.org/10.1016/j.bone.2018.01.008Get rights and content

Highlights

  • ā€¢

    BMAT expansion develops in a centripetal pattern during human and rodent lifespans.

  • ā€¢

    Amount of regulated BMAT changes dynamically in response to a wide variety of conditions. Constitutive BMAT is relatively stable.

  • ā€¢

    Local interactions between bone marrow adipocytes and cells of the marrow niche are complex and require further investigation.

  • ā€¢

    Proteins secreted from BMAT mediate functional interactions with cells near and afar.

Abstract

Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as ā€˜constitutiveā€™ and ā€˜regulatedā€™, respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells.

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 ā€œshifts 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.

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