Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues

Erica L. Scheller (), Casey R. Doucette, Brian S. Learman, William P. Cawthorn, Shaima Khandaker, Benjamin Schell, Brent Wu, Shi-Ying Ding, Miriam A. Bredella, Pouneh K. Fazeli, Basma Khoury, Karl J. Jepsen, Paul F. Pilch, Anne Klibanski, Clifford J. Rosen and Ormond A. MacDougald ()
Additional contact information
Erica L. Scheller: University of Michigan
Casey R. Doucette: Center for Clinical and Translational Research, Maine Medical Center Research Institute
Brian S. Learman: University of Michigan
William P. Cawthorn: University of Michigan
Shaima Khandaker: University of Michigan
Benjamin Schell: University of Michigan
Brent Wu: University of Michigan
Shi-Ying Ding: Boston University School of Medicine
Miriam A. Bredella: Massachusetts General Hospital and Harvard Medical School
Pouneh K. Fazeli: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School
Basma Khoury: University of Michigan
Karl J. Jepsen: University of Michigan
Paul F. Pilch: Boston University School of Medicine
Anne Klibanski: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School
Clifford J. Rosen: Center for Clinical and Translational Research, Maine Medical Center Research Institute
Ormond A. MacDougald: University of Michigan

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression and genetic determinants. Early MAT formation in mice is conserved, whereas later development is strain dependent. Proximal, but not distal tibial, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal ‘regulated’ MAT (rMAT) as single adipocytes interspersed with active haematopoiesis, whereas distal ‘constitutive’ MAT (cMAT) has low haematopoiesis, contains larger adipocytes, develops earlier and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, haematopoiesis and whole-body metabolism.

Date: 2015
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DOI: 10.1038/ncomms8808

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