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

Clarissa S Craft,William P Cawthorn,Hero Robles,Charles A Harris,Erica L Scheller,Kristann L Magee,Thomas L Andersen,Madelyn R Lorenz,Eric D Hilker,Ormond A Macdougald

doi:10.1038/s41598-019-54036-x

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.

Highlights

Adipocytes within the skeleton are collectively termed bone marrow adipose tissue (BMAT)
These cells are capable of lipid droplet remodeling in response to β3-agonist stimulation, BMAT lipid droplet remodeling is modest and morphologically distinct from ‘beige-like’ remodeling traditionally observed in white adipose tissues[7]
At 3-weeks of age, bone marrow adipocytes were nearly absent in the metaphyseal regions of the distal femur and the proximal metaphysis of the tibia

Summary

Introduction

Adipocytes within the skeleton are collectively termed bone marrow adipose tissue (BMAT). 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 This supports a paradigm by which BMAT adipocytes are a unique subpopulation that is specialized to support cells within the skeletal and hematopoietic niche. Regulated BMAT adipocytes reside in diverse, multicellular niches which can include pericytes, hematopoietic cells and osteogenic cells[11] These cells are capable of lipid droplet remodeling in response to β3-agonist stimulation, BMAT lipid droplet remodeling is modest and morphologically distinct from ‘beige-like’ remodeling traditionally observed in white adipose tissues[7]. It is clear that significant controversy exists in the literature regarding this point

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Conclusion