title: Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues.
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.
authors.affiliation: Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Scheller
authors.affiliation: Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
authors.forename: Casey R
authors.initials: CR
authors.lastname: Doucette
authors.affiliation: Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Learman
authors.affiliation: Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: William P
authors.identifier: http://orcid.org/0000-0001-7832-5057
authors.initials: WP
authors.lastname: Cawthorn
authors.affiliation: Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Shaima
authors.initials: S
authors.lastname: Khandaker
authors.affiliation: Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schell
authors.affiliation: Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Ding
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Bredella
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Pouneh K
authors.initials: PK
authors.lastname: Fazeli
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Basma
authors.initials: B
authors.lastname: Khoury
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Jepsen
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Pilch
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
authors.affiliation: Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.affiliation: Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Ormond A
authors.initials: OA
authors.lastname: MacDougald
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001853:Bone Marrow / Q000254:growth & development*; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D003080:Cold Temperature; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D066244:Proton Magnetic Resonance Spectroscopy; D016601:RNA-Binding Proteins / Q000502:physiology; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C112745:Cavin1 protein, mouse; D005227:Fatty Acids; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors