TY - JOUR
T1 - Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function
AU - Ortega, Francisco J.
AU - Moreno-Navarrete, José M.
AU - Mercader, Josep M.
AU - Gómez-Serrano, María
AU - García-Santos, Eva
AU - Latorre, Jèssica
AU - Lluch, Aina
AU - Sabater, Mònica
AU - Caballano-Infantes, Estefanía
AU - Guzmán, Rocío
AU - Macías-González, Manuel
AU - Buxo, Maria
AU - Gironés, Jordi
AU - Vilallonga, Ramon
AU - Naon, Deborah
AU - Botas, Patricia
AU - Delgado, Elias
AU - Corella, Dolores
AU - Burcelin, Remy
AU - Frühbeck, Gema
AU - Ricart, Wifredo
AU - Simó, Rafael
AU - Castrillon-Rodríguez, Ignacio
AU - Tinahones, Francisco J.
AU - Bosch, Fátima
AU - Vidal-Puig, Antonio
AU - Malagón, María M.
AU - Peral, Belén
AU - Zorzano, Antonio
AU - Fernández-Real, José M.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
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.
KW - Adipose Tissue/immunology
KW - Animals
KW - Blotting, Western
KW - Cytoskeleton/metabolism
KW - Diet, High-Fat/adverse effects
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Microfilament Proteins/genetics
KW - Muscle Proteins/genetics
KW - Obesity/etiology
KW - Sex Factors
KW - THP-1 Cells
U2 - 10.1096/fj.201900479R
DO - 10.1096/fj.201900479R
M3 - Article
C2 - 31145872
SN - 0892-6638
VL - 33
SP - 9656
EP - 9671
JO - FASEB Journal
JF - FASEB Journal
IS - 8
ER -
