MKK6 controls T3-mediated browning of white adipose tissue

Nuria Matesanz, Edgar Bernardo, Rebeca Acín-Pérez, Elisa Manieri, Sonia Pérez-Sieira, Lourdes Hernández-Cosido, Valle Montalvo-Romeral, Alfonso Mora, Elena Rodríguez, Luis Leiva-Vega, Ana Victoria Lechuga-Vieco, Jesús Ruiz-Cabello, Jorge L. Torres, Maria Crespo-Ruiz, Francisco Centeno, Clara V. Álvarez, Miguel Marcos, Jose Antonio Enríquez, Ruben Nogueiras and Guadalupe Sabio ()
Additional contact information
Nuria Matesanz: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Edgar Bernardo: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Rebeca Acín-Pérez: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Elisa Manieri: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Sonia Pérez-Sieira: University of Santiago de Compostela-Instituto de Investigación Sanitaria
Lourdes Hernández-Cosido: University of Salamanca
Valle Montalvo-Romeral: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Alfonso Mora: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Elena Rodríguez: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Luis Leiva-Vega: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Ana Victoria Lechuga-Vieco: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Jesús Ruiz-Cabello: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Jorge L. Torres: University Hospital of Salamanca-IBSAL
Maria Crespo-Ruiz: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Francisco Centeno: Grupo GIEN (Grupo de Investigación en Enfermedades Neurodegenerativas)
Clara V. Álvarez: University of Santiago de Compostela-Instituto de Investigación Sanitaria
Miguel Marcos: University Hospital of Salamanca-IBSAL
Jose Antonio Enríquez: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Ruben Nogueiras: University of Santiago de Compostela-Instituto de Investigación Sanitaria
Guadalupe Sabio: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00948-z

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