RT Journal Article
T1 The caveolae-associated coiled-coil protein, NECC2, regulates insulin signalling in Adipocytes.
A1 Travez, Andres
A1 Rabanal-Ruiz, Yoana
A1 Lopez-Alcala, Jaime
A1 Molero-Murillo, Laura
A1 Diaz-Ruiz, Alberto
A1 Guzman-Ruiz, Rocio
A1 Catalan, Victoria
A1 Rodriguez, Amaia
A1 Frühbeck, Gema
A1 Tinahones, Francisco J
A1 Gasman, Stephane
A1 Vitale, Nicolas
A1 Jimenez-Gomez, Yolanda
A1 Malagon, Maria M
K1 NECC2
K1 adipocytes
K1 adipogenesis
K1 caveolae
K1 insulin resistance
K1 insulin signalling
K1 obesity
AB 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.
PB Wiley-Blackwell Publishing Ltd.
YR 2018
FD 2018-07-13
LK http://hdl.handle.net/10668/12883
UL http://hdl.handle.net/10668/12883
LA en
NO Trávez A, Rabanal-Ruiz Y, López-Alcalá J, Molero-Murillo L, Díaz-Ruiz A, Guzmán-Ruiz R, et al. The caveolae-associated coiled-coil protein, NECC2, regulates insulin signalling in Adipocytes. J Cell Mol Med. 2018 Nov;22(11):5648-5661.
NO We dedicate this work to the bright memory of our colleague and friend Dr. Rafael Vázquez-Martínez. We thank Maria Ortega-Bellido (Dept. Cell Biology, Physiology and Immunology, Cordoba University, Spain) for her technical assistance.This work was supported by MINECO/FEDER (BFU2013-44229-R; BFU2017-90578-REDT; BFU2016-76711-R); Consejería de Salud y Bienestar Social/J. Andalucía/FEDER (PI-0200/2013); Instituto de Salud Carlos III (ISCIII) and Fondos FEDER (FIS PI12/00515, PI13/1430, PIE14/00005; Co-funded by European Regional Development Fund/European Social Fund “Investing in your future”); and Plan de Investigación de la Universidad de Navarra (PIUNA) (2011-2014). CIBEROBN is an initiative of ISCIII, Spain. AT, YJ-G, MMM conceived and designed the experiments. AT, YR-R, JL-A, LM-M, AD-R, RG-R, VC, AR, GF, YJ-G performed the experiments. AT, RG-R, FJT, YJ-G, MMM analysed the data. SG, NV, VC, AR, GF, FJT contributed reagents/materials/analysis tools. AT, YJ-G, MMM wrote the manuscript. All authors reviewed the paper and approved the final version of the manuscript.
DS RISalud
RD Apr 11, 2025