by Matesanz, Nuria, Bernardo, Edgar, Acín-Pérez, Rebeca, Manieri, Elisa, Pérez-Sieira, Sonia, Hernández-Cosido, Lourdes, Montalvo-Romeral, Valle, Mora, Alfonso, Rodríguez, Elena, Leiva-Vega, Luis, Lechuga-Vieco, Ana Victoria, Ruiz-Cabello, Jesus, Torres, Jorge L, Crespo-Ruiz, Maria, Centeno, Francisco, Álvarez, Clara V, Marcos, Miguel, Enríquez, José Antonio, Nogueiras, Ruben and Sabio, Guadalupe
Abstract:
Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity. Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6 in adipocytes as a potential therapeutic target to reduce obesity.Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.
Reference:
MKK6 controls T3-mediated browning of white adipose tissue. (Matesanz, Nuria, Bernardo, Edgar, Acín-Pérez, Rebeca, Manieri, Elisa, Pérez-Sieira, Sonia, Hernández-Cosido, Lourdes, Montalvo-Romeral, Valle, Mora, Alfonso, Rodríguez, Elena, Leiva-Vega, Luis, Lechuga-Vieco, Ana Victoria, Ruiz-Cabello, Jesus, Torres, Jorge L, Crespo-Ruiz, Maria, Centeno, Francisco, Álvarez, Clara V, Marcos, Miguel, Enríquez, José Antonio, Nogueiras, Ruben and Sabio, Guadalupe), In Nature Communications, Nature Publishing Group, volume 8, 2017.
Bibtex Entry:
@article{Matesanz:2017dj,
author = {Matesanz, Nuria and Bernardo, Edgar and Ac{'i}n-P{'e}rez, Rebeca and Manieri, Elisa and P{'e}rez-Sieira, Sonia and Hern{'a}ndez-Cosido, Lourdes and Montalvo-Romeral, Valle and Mora, Alfonso and Rodr{'i}guez, Elena and Leiva-Vega, Luis and Lechuga-Vieco, Ana Victoria and Ruiz-Cabello, Jesus and Torres, Jorge L and Crespo-Ruiz, Maria and Centeno, Francisco and {'A}lvarez, Clara V and Marcos, Miguel and Enr{'i}quez, Jos{'e} Antonio and Nogueiras, Ruben and Sabio, Guadalupe},
title = {{MKK6 controls T3-mediated browning of white adipose tissue.}},
journal = {Nature Communications},
year = {2017},
volume = {8},
number = {1},
pages = {856},
month = oct,
publisher = {Nature Publishing Group},
affiliation = {Fundaci{'o}n Centro Nacional de Investigaciones Cardiovasculares Carlos III, Calle Melchor Fern{'a}ndez Almagro, 3, 28029, Madrid, Spain.},
doi = {10.1038/s41467-017-00948-z},
pmid = {29021624},
pmcid = {PMC5636784},
language = {English},
rating = {0},
date-added = {2017-11-14T14:58:43GMT},
date-modified = {2018-11-22T21:14:03GMT},
abstract = {Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity. Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6 in adipocytes as a potential therapeutic target to reduce obesity.Brown and beige adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors show that the stress activated kinase MKK6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure.},
url = {http://www.nature.com/articles/s41467-017-00948-z},
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uri = {url{papers3://publication/doi/10.1038/s41467-017-00948-z}}
}