The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism

• Published in: Diabetologia 2017-02, Vol.60 (2), p.324-335
• Main Authors: Moreno-Castellanos, Natalia, Rodríguez, Amaia, Rabanal-Ruiz, Yoana, Fernández-Vega, Alejandro, López-Miranda, José, Vázquez-Martínez, Rafael, Frühbeck, Gema, Malagón, María M.
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - metabolism; Adult; Body fat; Caveolae - metabolism; Cytoskeleton; Diabetes; Fatty Acid-Binding Proteins - genetics; Fatty Acid-Binding Proteins - metabolism; Fatty acids; Female; Gene Silencing - physiology; Glucose; Human Physiology; Humans; Immunoblotting; Immunohistochemistry; Insulin resistance; Insulin Resistance - genetics; Insulin Resistance - physiology; Internal Medicine; Kinases; Lipid Metabolism - genetics; Lipid Metabolism - physiology; Lipids; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Middle Aged; Obesity; Obesity - genetics; Obesity - metabolism; Proteins; Real-Time Polymerase Chain Reaction; Septins - genetics; Septins - metabolism
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-016-4155-5

Aims/hypothesis 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. Methods 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. Results 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. Conclusions/interpretation 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.