title: De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific.
abstract: It is generally assumed that white adipocytes arise from resident adipose tissue mesenchymal progenitor cells. We challenge this paradigm by defining a hematopoietic origin for both the de novo development of a subset of white adipocytes in adults and a previously uncharacterized adipose tissue resident mesenchymal progenitor population. Lineage and cytogenetic analysis revealed that bone marrow progenitor (BMP)-derived adipocytes and adipocyte progenitors arise from hematopoietic cells via the myeloid lineage in the absence of cell fusion. Global gene expression analysis indicated that the BMP-derived fat cells are bona fide adipocytes but differ from conventional white or brown adipocytes in decreased expression of genes involved in mitochondrial biogenesis and lipid oxidation, and increased inflammatory gene expression. The BMP-derived adipocytes accumulate with age, occur in higher numbers in visceral than in subcutaneous fat, and in female versus male mice. BMP-derived adipocytes may, therefore, account in part for adipose depot heterogeneity and detrimental changes in adipose metabolism and inflammation with aging and adiposity.
authors.affiliation: Charles C Gates Regenerative Medicine and Stem Cell Biology Program, Department of Pediatrics, Cardiovascular Pulmonary Research Laboratory, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Majka
authors.forename: Keith E
authors.initials: KE
authors.lastname: Fox
authors.forename: John C
authors.initials: JC
authors.lastname: Psilas
authors.forename: Karen M
authors.initials: KM
authors.lastname: Helm
authors.forename: Christine R
authors.initials: CR
authors.lastname: Childs
authors.forename: Alistaire S
authors.initials: AS
authors.lastname: Acosta
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Janssen
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Friedman
authors.forename: Brian T
authors.initials: BT
authors.lastname: Woessner
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Shade
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Dwight J
authors.initials: DJ
authors.lastname: Klemm
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism; D052438:Adipocytes, White / Q000166:cytology* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D020732:Cytogenetic Analysis; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012737:Sex Factors