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

Moreno-Castellanos, Natalia; Rodríguez, Amaia; Rabanal-Ruíz, Yoana; Fernández-Vega, Alejandro; López‐Miranda, José; Vázquez-Martı́nez, Rafael; Frühbeck, Gema; Malagón, Marı́a M.

doi:10.1007/s00125-016-4155-5

Cited by 28 publications

(35 citation statements)

References 47 publications

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“…Furthermore, septin-11 was found to be expressed in human adipocytes and upregulated in obese individuals. SEPT11 mRNA was positively correlated with markers of insulin resistance in adipose tissue, and silencing of septin-11 muted insulin signaling and insulin-induced lipid accumulation in adipocytes [40].…”

Section: Discussionmentioning

confidence: 99%

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

et al. 2019

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Epithelial Ovarian Cancer (EOC) is associated with dismal survival rates due to the fact that patients are frequently diagnosed at an advanced stage and eventually become resistant to traditional chemotherapeutics. Hence, there is a crucial need for new and innovative therapies. Septin-2, a member of the septin family of GTP binding proteins, has been characterized in EOC for the first time and represents a potential future target. Septin-2 was found to be overexpressed in serous and clear cell human patient tissue compared to benign disease. Stable septin-2 knockdown clones developed in an ovarian cancer cell line exhibited a significant decrease in proliferation rates. Comparative label-free proteomic analysis of septin-2 knockdown cells revealed differential protein expression of pathways associated with the TCA cycle, acetyl CoA, proteasome and spliceosome. Further validation of target proteins indicated that septin-2 plays a predominant role in post-transcriptional and translational modifications as well as cellular metabolism, and suggested the potential novel role of septin-2 in promoting EOC tumorigenesis through these mechanisms.

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Section: Discussionmentioning

confidence: 99%

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

et al. 2019

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“…3T3‐L1 cells [American Type Culture Collection (Manassas, VA, USA)] were differentiated into adipocytes as previously described 22,26 . Briefly, 3T3‐L1 cells were cultured onto 6‐ or 12‐well plates (3 × 10 3 cells/cm 2 ) or glass coverslips (2 × 10 3 cells/cm 2 ) in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% of newborn calf serum, 4 mM of glutamine, and 1% of antibiotic‐antimycotic solution.…”

Section: Methodsmentioning

confidence: 99%

Adipose tissue depot‐specific intracellular and extracellular cues contributing to insulin resistance in obese individuals

et al. 2020

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Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose tissue dysfunction in obesity are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) and omental (OM) fat from lean subjects and obese individuals with different degrees of insulin sensitivity was performed to identify adipose tissue biomarkers related to obesity‐associated metabolic disease. Our results suggest that dysregulation of both adipose tissue extracellular matrix (ECM) organization and intracellular trafficking processes may be associated with IR in obesity. Thus, abnormal accumulation of the small leucine‐rich proteoglycan, lumican, as observed in SC fat of IR obese individuals, modifies collagen I organization, impairs adipogenesis and activates stress processes [endoplasmic reticulum and oxidative stress] in adipocytes. In OM fat, IR is associated with increased levels of the negative regulator of the Rab family of small GTPases, GDI2, which alters lipid storage in adipocytes by inhibiting insulin‐stimulated binding of the Rab protein, Rab18, to lipid droplets. Together, these results indicate that lumican and GDI2 might play depot‐dependent, pathogenic roles in obesity‐associated IR. Our findings provide novel insights into the differential maladaptive responses of SC and OM adipose tissue linking obesity to IR.

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“…We further examine the association of NECC2 with CAV1 by co‐immunoprecipitation analysis, which revealed the interaction between these two proteins (Figure A and Figure ). However, when we employed a detergent‐free method to isolate caveolin‐enriched membrane fractions, we found that endogenous NECC2, at least the variant identified by the anti‐NECC2 antibody employed herein, did not co‐migrate with CAV1, Cavin1 or IR to “buoyant” fractions (Figure B). Notably, the Na 2 CO 3 lysis buffer employed in this protocol for protein isolation maintains integral but not soluble and peripheral membrane proteins .…”

Section: Resultsmentioning

confidence: 88%

“…A standard protocol was used for co‐immunoprecipitation of NECC2 and CAV1 in HEK‐293 AD cells transfected with c‐Myc‐ Necc2 and CFP‐ Cav1 as described previously …”

Section: Methodsmentioning

confidence: 99%

The caveolae‐associated coiled‐coil protein, NECC2, regulates insulin signalling in Adipocytes

Trávez

López-Alcalá

Molero‐Murillo

et al. 2018

J Cellular Molecular Medi

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Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated by large complexes of caveolin and cavin proteins, along with proteins with membrane‐binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2 (NECC2), in adipocytes. Studies in 3T3‐L1 cells showed that NECC2 expression increased during adipogenesis. Furthermore, NECC2 co‐immunoprecipitated with caveolin‐1 (CAV1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin. Interestingly, NECC2 overexpression enhanced insulin‐activated Akt phosphorylation, whereas NECC2 downregulation impaired insulin‐induced phosphorylation of Akt and ERK2. Finally, an up‐regulation of NECC2 in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies NECC2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.

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

Abstract: 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.

Cited by 28 publications

References 47 publications

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

Septin-2 is overexpressed in epithelial ovarian cancer and mediates proliferation via regulation of cellular metabolic proteins

Adipose tissue depot‐specific intracellular and extracellular cues contributing to insulin resistance in obese individuals

The caveolae‐associated coiled‐coil protein, NECC2, regulates insulin signalling in Adipocytes

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