RT Journal Article
T1 Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.
A1 Ortega, Francisco J
A1 Moreno-Navarrete, Jose M
A1 Mercader, Josep M
A1 Gomez-Serrano, Maria
A1 Garcia-Santos, Eva
A1 Latorre, Jessica
A1 Lluch, Aina
A1 Sabater, Monica
A1 Caballano-Infantes, Estefania
A1 Guzman, Rocio
A1 Macias-Gonzalez, Manuel
A1 Buxo, Maria
A1 Girones, Jordi
A1 Vilallonga, Ramon
A1 Naon, Deborah
A1 Botas, Patricia
A1 Delgado, Elias
A1 Corella, Dolores
A1 Burcelin, Remy
A1 Frühbeck, Gema
A1 Ricart, Wifredo
A1 Simo, Rafael
A1 Castrillon-Rodriguez, Ignacio
A1 Tinahones, Francisco J
A1 Bosch, Fatima
A1 Vidal-Puig, Antonio
A1 Malagon, Maria M
A1 Peral, Belen
A1 Zorzano, Antonio
A1 Fernandez-Real, Jose M
K1 Adipocytes
K1 Cytoskeleton
K1 Inflammation
K1 Obesity
AB During adipogenesis, preadipocytes' cytoskeleton reorganizes in parallel with lipid accumulation. Failure to do so may impact the ability of adipose tissue (AT) to shift between lipid storage and mobilization. Here, we identify cytoskeletal transgelin 2 (TAGLN2) as a protein expressed in AT and associated with obesity and inflammation, being normalized upon weight loss. TAGLN2 was primarily found in the adipose stromovascular cell fraction, but inflammation, TGF-β, and estradiol also prompted increased expression in human adipocytes. Tagln2 knockdown revealed a key functional role, being required for proliferation and differentiation of fat cells, whereas transgenic mice overexpressing Tagln2 using the adipocyte protein 2 promoter disclosed remarkable sex-dependent variations, in which females displayed "healthy" obesity and hypertrophied adipocytes but preserved insulin sensitivity, and males exhibited physiologic changes suggestive of defective AT expandability, including increased number of small adipocytes, activation of immune cells, mitochondrial dysfunction, and impaired metabolism together with decreased insulin sensitivity. The metabolic relevance and sexual dimorphism of TAGLN2 was also outlined by genetic variants that may modulate its expression and are associated with obesity and the risk of ischemic heart disease in men. Collectively, current findings highlight the contribution of cytoskeletal TAGLN2 to the obese phenotype in a gender-dependent manner.-Ortega, F. J., Moreno-Navarrete, J. M., Mercader, J. M., Gómez-Serrano, M., García-Santos, E., Latorre, J., Lluch, A., Sabater, M., Caballano-Infantes, E., Guzmán, R., Macías-González, M., Buxo, M., Gironés, J., Vilallonga, R., Naon, D., Botas, P., Delgado, E., Corella, D., Burcelin, R., Frühbeck, G., Ricart, W., Simó, R., Castrillon-Rodríguez, I., Tinahones, F. J., Bosch, F., Vidal-Puig, A., Malagón, M. M., Peral, B., Zorzano, A., Fernández-Real, J. M. Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function.
PB Wiley
YR 2019
FD 2019-04-29
LK http://hdl.handle.net/10668/14041
UL http://hdl.handle.net/10668/14041
LA en
NO Ortega FJ, Moreno-Navarrete JM, Mercader JM, Gómez-Serrano M, García-Santos E, Latorre J, et al. Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function. FASEB J. 2019 Aug;33(8):9656-9671
NO The work of all the members of the Multidisciplinary Obesity Team of the Cl´ınica Universitaria de Navarra is gratefully acknowledged. The authors are indebted to the Institut d’Investigacio Biomédica de Girona (IDIBGI) Bio- `bank, integrated in the Spanish National Biobank Network, for the sample and data procurement. GenDiab Consortium was constituted with funds from the Ministerio de Educacion y Ciencia (Grant GEN2001-4758). This work was also supported by research funds from the Instituto de Salud Carlos III(ISCIII; PI15/01934 to J.M.F-R., and PI18/00550 to F.J.O.) and the Ministerio de Educacion y Ciencia (SAF2008-02073 to J.M.F.-R., SAF2009-10461 and SAF2012-33014 to B.P.), the Instituto de Salud Carlos III (CIBEROBN and CIBERDEM), the Pla estrategic de recerca i innovacio en salut and the Govern de la Generalitat (PERIS 2016 to F.J.O.), the Agencia de Gestio ’Ajuts Universitaris de Recerca (AGAUR, FI-DGR 2015 to J.L.), the Universidad Autonoma de Madrid (FPI-UAM to M.G.-S.), and the Fondo Europeo de Desarrollo Regional (FEDER). J.M.M. was supported by a Beatriu de Pinos´fellowship from the AGAUR. R.B. is recipient of funding from the Agence Nationale de la Recherche (Florinflam and Floradip programs) and the Institute Nationale du Diabete. The authors declare no conflicts of interest.
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RD Apr 17, 2025