MKK6 controls T3-mediated browning of white adipose tissue

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MKK6 controls T3-mediated browning of white adipose tissue

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Title: MKK6 controls T3-mediated browning of white adipose tissue
Author: Matesanz Parellada, Nuria; Bernardo Vasco, Edgar; Acín Pérez, Rebeca; Manieri, Elisa; Pérez Sieira, Sonia; Hernández Cosido, Lourdes; Montalvo Romeral, Valle; Mora Corral, Alfonso; Rodríguez Vieítez, Elena; Leiva Vega, Luis; Lechuga Vieco, Ana Victoria; Ruiz Cabello, Jesús; Torres Triana, Jorge Luis; Crespo Ruiz-Cabello, Maria; Centeno Velázquez, Francisco; Álvarez Villamarín, Clara; Marcos Martín, Miguel; Enríquez Domínguez, José Antonio; Nogueiras Pozo, Ruben; Sabio Buzo, Guadalupe
Abstract: El aumento de la capacidad termogénica del tejido adiposo para mejorar el gasto de energía del organismo se considera una estrategia terapéutica prometedora para combatir la obesidad. Aquí nosotros informe que la expresión del activador MAPK p38 MKK6 está elevada en el tejido adiposo blanco de individuos obesos. Usando animales knockout y shRNA, mostramos que la eliminación de Mkk6 aumenta el gasto de energía y la capacidad termogénica del tejido adiposo blanco, protegiendo a los ratones contra la obesidad inducida por la dieta y el desarrollo de la diabetes. La eliminación de Mkk6 aumenta la expresión de UCP1 estimulada por T3 en los adipocitos, lo que aumenta su capacidad termogénica. De manera mecánica, demostramos que, en el tejido adiposo blanco, p38 se activa mediante una ruta alternativa que involucra AMPK, TAK y TAB. Nuestros resultados identifican MKK6 en los adipocitos como un posible objetivo terapéutico para reducir la obesidad.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.
URI: http://hdl.handle.net/10662/9002
Date: 2017


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