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

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  • Erica L. Scheller

    (University of Michigan
    Present address: Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University, Saint Louis, Missouri 63110, USA.)

  • 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)

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.

Suggested Citation

  • 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 & , 2015. "Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8808
    DOI: 10.1038/ncomms8808
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    Cited by:

    1. Tammy Liu & Gerd Melkus & Tim Ramsay & Adnan Sheikh & Odette Laneuville & Guy Trudel, 2023. "Bone marrow adiposity modulation after long duration spaceflight in astronauts," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. N. Zioni & A. Akhiad Bercovich & N. Chapal-Ilani & Tal Bacharach & N. Rappoport & A. Solomon & R. Avraham & E. Kopitman & Z. Porat & M. Sacma & G. Hartmut & M. Scheller & C. Muller-Tidow & D. Lipka & , 2023. "Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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