title: The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism.
abstract: Septins are newly identified members of the cytoskeleton that have been proposed as biomarkers of a number of diseases. However, septins have not been characterised in adipose tissue and their relationship with obesity and insulin resistance remains unknown. Herein, we characterised a member of this family, septin 11 (SEPT11), in human adipose tissue and analysed its potential involvement in the regulation of adipocyte metabolism.
  
  
  
  Gene and protein expression levels of SEPT11 were analysed in human adipose tissue. SEPT11 distribution was evaluated by immunocytochemistry, electron microscopy and subcellular fractionation techniques. Glutathione S-transferase (GST) pull-down, immunoprecipitation and yeast two-hybrid screening were used to identify the SEPT11 interactome. Gene silencing was used to assess the role of SEPT11 in the regulation of insulin signalling and lipid metabolism in adipocytes.
  
  
  
  We demonstrate the expression of SEPT11 in human adipocytes and its upregulation in obese individuals, with SEPT11 mRNA content positively correlating with variables of insulin resistance in subcutaneous adipose tissue. SEPT11 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human adipocytes. SEPT11 associated with caveolae in mature adipocytes and interacted with both caveolin-1 and the intracellular fatty acid chaperone, fatty acid binding protein 5 (FABP5). Lipid loading of adipocytes caused the association of the three proteins with the surface of lipid droplets. SEPT11 silencing impaired insulin signalling and insulin-induced lipid accumulation in adipocytes.
  
  
  
  Our findings support a role for SEPT11 in lipid traffic and metabolism in adipocytes and open new avenues for research on the control of lipid storage in obesity and insulin resistance.
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital, Edificio IMIBIC, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Moreno-Castellanos
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain.|Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital, Edificio IMIBIC, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain.
authors.forename: Yoana
authors.initials: Y
authors.lastname: Rabanal-Ruiz
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital, Edificio IMIBIC, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Fernández-Vega
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain.|Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Córdoba, Córdoba, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López-Miranda
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital, Edificio IMIBIC, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vázquez-Martínez
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain, . gfruhbeck@unav.es.|Metabolic Research Laboratory, Clínica Universidad de Navarra, IdiSNA, Pamplona, Spain. gfruhbeck@unav.es.|Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Avda. Pío XII 36, 31008, Pamplona, Spain. gfruhbeck@unav.es.
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital, Edificio IMIBIC, Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain. bc1mapom@uco.es.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain. bc1mapom@uco.es.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Spain, . bc1mapom@uco.es.
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D021941:Caveolae / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D058112:Septins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; C496549:SEPTIN11 protein, human; D058112:Septins
keywords: Caveolae; FABP5; Lipid droplets; Lipid metabolism; Obesity; Septins