title: Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source.
abstract: Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric, and it is a subject of much debate whether these have a common developmental origin and whether this differs from that for subcutaneous WAT. Here we show that all six visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue arises from Wt1-expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1-expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show that all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated, and provide several lines of evidence that Wt1-expressing mesothelium can produce adipocytes. These results reveal a major ontogenetic difference between visceral and subcutaneous WAT, and pinpoint the lateral plate mesoderm as a major source of visceral WAT. They also support the notion that visceral WAT progenitors are heterogeneous, and suggest that mesothelium is a source of adipocytes.
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Crewe Road Edinburgh EH4 2XU, UK.
authors.forename: You-Ying
authors.initials: YY
authors.lastname: Chau
authors.affiliation: IBV, INSERM U1091, Université de Nice Sophia-Antipolis, Parc Valrose, Centre de Biochimie 06100 Nice Cedex-2, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bandiera
authors.affiliation: Institute for Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh Cancer Research UK Centre, Western General Hospital Campus, Crewe Road South Edinburgh EH4 2XR, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Serrels
authors.affiliation: Department of Cell Biology, Faculty of Biology, University of Barcelona, Av. Diagonal, 643 08028 Barcelona, Spain.
authors.forename: Ofelia M
authors.initials: OM
authors.lastname: Martínez-Estrada
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Crewe Road Edinburgh EH4 2XU, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Qing
authors.affiliation: Institute for Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh Cancer Research UK Centre, Western General Hospital Campus, Crewe Road South Edinburgh EH4 2XR, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Lee
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Crewe Road Edinburgh EH4 2XU, UK.
authors.forename: Joan
authors.initials: J
authors.lastname: Slight
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Crewe Road Edinburgh EH4 2XU, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Thornburn
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Crewe Road Edinburgh EH4 2XU, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Berry
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Crewe Road Edinburgh EH4 2XU, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: McHaffie
authors.affiliation: BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stimson
authors.affiliation: BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: Department of Animal Biology, University of Málaga, E29071 Málaga, Spain.
authors.forename: Ramon Muñoz
authors.initials: RM
authors.lastname: Chapuli
authors.affiliation: IBV, INSERM U1091, Université de Nice Sophia-Antipolis, Parc Valrose, Centre de Biochimie 06100 Nice Cedex-2, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schedl
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Crewe Road Edinburgh EH4 2XU, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Hastie
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D019070:Cell Lineage / Q000235:genetics; D055879:Gene Knock-In Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D013629:Tamoxifen / Q000494:pharmacology; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D025721:WT1 Proteins; D013629:Tamoxifen; D049452:Green Fluorescent Proteins