Development, regulation, metabolism and function of bone marrow adipose tissues

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 'constitutive' and 'regulated', 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.

Exercise Degrades Bone in Caloric Restriction, Despite Suppression of Marrow Adipose Tissue (MAT)

“…(3,72) Increased glucocorticoids, Pref-1, and MAT-derived adiponectin (28,73,74) as well as low IGF-1 and leptin (28,32,(75)(76)(77) have been associated with MAT in CR; however, causality has not been established for these factors in driving MAT nor in the skeletal deterioration of CR. (3,72) Increased glucocorticoids, Pref-1, and MAT-derived adiponectin (28,73,74) as well as low IGF-1 and leptin (28,32,(75)(76)(77) have been associated with MAT in CR; however, causality has not been established for these factors in driving MAT nor in the skeletal deterioration of CR.…”

“…The mechanisms by which MAT accrues in the calorie-restricted state continue to be an area of active investigation. (3,72) Increased glucocorticoids, Pref-1, and MAT-derived adiponectin (28,73,74) as well as low IGF-1 and leptin (28,32,(75)(76)(77) have been associated with MAT in CR; however, causality has not been established for these factors in driving MAT nor in the skeletal deterioration of CR. Systemic sclerostin inhibition was shown to reduce marrow adipocytes.…”

G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche

“…There is increasing appreciation of important functional interactions between bone cells and other cell types within the marrow niche such as bone marrow adipocytes and hematopoietic cells (16,17). Bone marrow is an enclosed system, and thus expansion of one cell type is often at the expense of others (16).…”

Mapping and targeting of the leukemic microenvironment

“…Maintenance of osteoblast numbers during leukemia by pharmacological inhibition of the synthesis of duodenal serotonin through treatment with a tryptophan hydroxylase inhibitor stimulates normal hematopoiesis, delays disease engraftment, reduces tumor burden, and prolongs survival (Krevvata et al, 2014). Castillo et al, 2016;Castillo et al, 2012;Orgel et al, 2016;Orgel et al, 2014 Sequester and metabolize commonly used chemotherapeutic drugs Behan et al, 2009;Pramanik et al, 2013;Sheng et al, 2017Sheng et al, 2017 Secrete glutamine: inhibits the activity of L-asparaginase, a common treatment for ALL Ehsanipour et al, 2013 Fuel AML blasts survival by production of free fatty acids Shafat et al, 2017;Ye et al, 2016;Li et al, 2018Shafat et al, 2017 Lepr + Esm1 + perivascular cells…”