RT Journal Article
T1 The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism.
A1 Moreno-Castellanos, Natalia
A1 Rodriguez, Amaia
A1 Rabanal-Ruiz, Yoana
A1 Fernandez-Vega, Alejandro
A1 Lopez-Miranda, Jose
A1 Vazquez-Martinez, Rafael
A1 Fruhbeck, Gema
A1 Malagon, Maria M.
K1 Caveolae
K1 FABP5
K1 Lipid droplets
K1 Lipid metabolism
K1 Obesity
K1 Septins
AB 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.
PB Springer
YR 2016
FD 2016-10-25
LK http://hdl.handle.net/10668/10619
UL http://hdl.handle.net/10668/10619
LA en
NO Moreno-Castellanos N, Rodríguez A, Rabanal-Ruiz Y, Fernández-Vega A, López-Miranda J, Vázquez-Martínez R, et al. The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism. Diabetologia. 2017 Feb;60(2):324-335
DS RISalud
RD Apr 7, 2025