title: Membrane and nuclear estrogen receptor α collaborate to suppress adipogenesis but not triglyceride content.
abstract: Estrogen and estrogen receptor (ER)-α suppress visceral fat development through actions in several organs via unclear mechanisms that we sought to identify. Using mice that express only nuclear ER-α [nuclear-only ER-α (NOER) mice] or plasma membrane ER-α [membrane-only ER-α (MOER) mice], we found that 10-wk-old mice that lacked either receptor pool showed extensive abdominal visceral fat deposition and weight gain compared with wild-type (WT) mice. Differentiation of cultured bone marrow stem cells (BMSCs) into the adipocyte lineage was suppressed by 17-β-estradiol (E2) in WT female mice but not in NOER or MOER mice. This finding correlated with E2 inhibition of prominent differentiation genes in WT BMSCs. In contrast, triglyceride content in differentiated BMSCs or 3T3-L1 cells was suppressed as a result of membrane ER-α signaling through several kinases to inhibit carbohydrate response element-binding protein-α and -β. We concluded that extranuclear and nuclear ER-α collaborate to suppress adipocyte development, but inhibition of lipid synthesis in mature cells does not involve nuclear ER-α.
authors.affiliation: *Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California, USA; Department of Developmental and Cell Biology, Department of Medicine, and Department of Biochemistry, University of California, Irvine, Irvine, California, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Pedram
authors.affiliation: *Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California, USA; Department of Developmental and Cell Biology, Department of Medicine, and Department of Biochemistry, University of California, Irvine, Irvine, California, USA.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Razandi
authors.affiliation: *Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California, USA; Department of Developmental and Cell Biology, Department of Medicine, and Department of Biochemistry, University of California, Irvine, Irvine, California, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Blumberg
authors.affiliation: *Division of Endocrinology, Veterans Affairs Medical Center, Long Beach, California, USA; Department of Developmental and Cell Biology, Department of Medicine, and Department of Biochemistry, University of California, Irvine, Irvine, California, USA ellis.levin@va.gov.
authors.forename: Ellis Robert
authors.initials: ER
authors.lastname: Levin
mesh_terms: D050156:Adipogenesis; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D047628:Estrogen Receptor alpha; D014280:Triglycerides; D004958:Estradiol
keywords: BMSCs; ChREBP; adipocyte hypertrophy; kinase activation; preadipocytes