title: Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells.
abstract: Oestrogen, often via oestrogen receptor alpha (ERα) signalling, regulates metabolic physiology, highlighted by post-menopausal temperature dysregulation (hot flashes), glucose intolerance, increased appetite and reduced metabolic rate. Here we show that ERα signalling has a role in adipose lineage specification in mice. ERα regulates adipose progenitor identity and potency, promoting white adipogenic lineage commitment. White adipose progenitors lacking ERα reprogramme and enter into smooth muscle and brown adipogenic fates. Mechanistic studies highlight a TGFβ programme involved in progenitor reprogramming downstream of ERα signalling. The observed reprogramming has profound metabolic outcomes; both female and male adipose-lineage ERα-mutant mice are lean, have improved glucose sensitivity and are resistant to weight gain on a high-fat diet. Further, they are hypermetabolic, hyperphagic and hyperthermic, all consistent with a brown phenotype. Together, these findings indicate that ERα cell autonomously regulates adipose lineage commitment, brown fat and smooth muscle cell formation, and systemic metabolism, in a manner relevant to prevalent metabolic diseases.
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9133, USA.
authors.forename: Kfir
authors.initials: K
authors.lastname: Lapid
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9133, USA.
authors.forename: Ajin
authors.initials: A
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9133, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Clegg
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9133, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zeve
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9133, USA.|Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9133, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Graff
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D002001:Adipose Tissue, Brown / Q000166:cytology*; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011897:Random Allocation; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins