title: PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors.
abstract: The developmental origin of adipose tissue and what controls its distribution is poorly understood. By lineage tracing and gene expression analysis in mice, we provide evidence that mesenchymal precursors expressing Myf5--which are thought to give rise only to brown adipocytes and skeletal muscle--also give rise to a subset of white adipocytes. Furthermore, individual brown and white fats contain a mixture of adipocyte progenitor cells derived from Myf5(+) and Myf5(neg) lineages, the number of which varies with depot location. Subsets of white adipocytes originating from both Myf5(+) and Myf5(neg) precursors respond to β(3)-adrenoreceptor stimulation, suggesting "brite" adipocytes may also have multiple origins. We additionally find that deleting PTEN with myf5-cre causes lipomatosis and partial lipodystrophy by selectively expanding the Myf5(+) adipocyte lineages. Thus, the spectrum of adipocytes arising from Myf5(+) precursors is broader than previously thought, and differences in PI3K activity between adipocyte lineages alter body fat distribution.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Sanchez-Gurmaches
authors.forename: Chien-Min
authors.initials: CM
authors.lastname: Hung
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Sparks
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Tang
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
authors.forename: David A
authors.initials: DA
authors.lastname: Guertin
mesh_terms: D052438:Adipocytes, White / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins; D050218:Body Fat Distribution; D002454:Cell Differentiation / Q000502:physiology*; D005434:Flow Cytometry; D006652:Histological Techniques; D008068:Lipomatosis / Q000378:metabolism; D008164:Luminescent Proteins; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000172:deficiency*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D022702:Receptors, Adrenergic, beta-3; C054562:yellow fluorescent protein, Bacteria; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse