Bone marrow adipose tissue does not express UCP1 during development or adrenergic-induced remodeling

Abstract

Adipocytes within the skeleton are collectively termed bone marrow adipose tissue (BMAT). BMAT contributes to peripheral and local metabolism, however, its capacity for cell-autonomous expression of uncoupling protein 1 (UCP1), a biomarker of beige and brown adipogenesis, remains unclear. To overcome this, Ucp1-Cre was used to drive diphtheria toxin expression in cells expressing UCP1 (Ucp1Cre+/DTA+). Despite loss of brown adipose tissue, BMAT volume was not reduced in Ucp1Cre+/DTA+ mice. Comparably, in mTmG reporter mice (Ucp1Cre+/mTmG+), Ucp1-Cre expression was absent from BMAT in young (3-weeks) and mature (16-weeks) male and female mice. Further, β3-agonist stimulation failed to induce Ucp1-Cre expression in BMAT. This demonstrates that BMAT adipocytes are not UCP1-expressing beige/brown adipocytes. Thus, to identify novel and emerging roles for BMAT adipocytes in skeletal and whole-body homeostasis, we performed gene enrichment analysis of microarray data from adipose tissues of adult rabbits. Pathway analysis revealed genetic evidence for differences in BMAT including insulin resistance, decreased fatty acid metabolism, and enhanced contributions to local processes including bone mineral density through candidate genes such as osteopontin. In sum, this supports a paradigm by which BMAT adipocytes are a unique subpopulation that is specialized to support cells within the skeletal and hematopoietic niche.

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis

“…Similarly, microarrays show that UCP1 is not enriched in whole BM of mice or humans 35,36 , nor is it greater in BMAds vs white adipocytes of mice 37 . Consistent with this, recent work using lineage tracing and genetic models has convincingly demonstrated that BMAds do not express Ucp1 during development or after adrenergic stimulation in mice 41 . Moreover, BMAd progenitors are more white-like than brownlike and do not express brown adipocyte markers after adipogenesis in vitro 42 .…”

A novel skeletal-specific adipogenesis pathway defines key origins and adaptations of bone marrow adipocytes with age and disease

“…It has previously been assumed that all adipocytes, including bone marrow adipocytes, express the adipokine adiponectin (15,21,22). And, conversely, that adiponectin is not expressed by cells that are not adipocytes.…”

Standardised Nomenclature, Abbreviations, and Units for the Study of Bone Marrow Adiposity: Report of the Nomenclature Working Group of the International Bone Marrow Adiposity Society

“…Indeed, microarrays show that UCP1 transcripts are not enriched in whole BM of mice or humans (104,105), nor is Ucp1 expression greater in BMAds vs. white adipocytes of mice (106). Recent work using lineage tracing and genetic models has also demonstrated that BMAds do not express Ucp1 during development or after adrenergic stimulation in mice (107). Similarly, primary BMAd progenitors have very limited, if any, brown adipogenic potential (89), and BMAds in vivo Data are presented as described for Table 7, except that imaging method is also indicated.…”

“…do not undergo cold-induced glucose uptake (108). However, multilocular BMAds do exist and account for around 5% of all BMAds in the long bones of mice (107). Thus, while it seems that BM adipocytes are distinct from brown adipocytes, it is unlikely that this multilocularity is indeed equated to brown adipocyte-like functions of BMAds.…”