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Tag: p38δ (page 1 of 2)

p38α blocks brown adipose tissue thermogenesis through p38δ inhibition

Nuria Matesanz, Ivana Nikolić, Magdalena Leiva, Marta Pulgarín-Alfaro, Ayelén M. Santamans, Edgar Bernardo, Alfonso Mora, Leticia Herrera-Melle, Elena Rodríguez, Daniel Beiroa, Ainoa Caballero, Elena Martín-García, Rebeca Acín-Pérez, Lourdes Hernández-Cosido, Luis Leiva-Vega, Jorge L. Torres, Francisco Centeno, Angel R. Nebreda, José Antonio Enríquez, Rubén Nogueiras, Miguel Marcos & Guadalupe Sabio.

Adipose tissue has emerged as an important regulator of whole-body metabolism, and its capacity to dissipate energy in the form of heat has acquired a special relevance in recent years as potential treatment for obesity. In this context, the p38MAPK pathway has arisen as a key player in the thermogenic program because it is required for the activation of brown adipose tissue (BAT) thermogenesis and participates also in the transformation of white adipose tissue (WAT) into BAT-like depot called beige/brite tissue.

Regulation of browning and BAT activation by p38 pathway (Image: Ivana Nikolić).

Here, using mice that are deficient in p38α specifically in adipose tissue (p38αFab-KO), we unexpectedly found that lack of p38α protected against high-fat diet (HFD)-induced obesity. We also showed that p38αFab-KO mice presented higher energy expenditure due to increased BAT thermogenesis. Mechanistically, we found that lack of p38α resulted in the activation of the related protein kinase family member p38δ.

Our results showed that p38δ is activated in BAT by cold exposure, and lack of this kinase specifically in adipose tissue (p38δFab-KO) resulted in overweight together with reduced energy expenditure and lower body and skin surface temperature in the BAT region. These observations indicate that p38α probably blocks BAT thermogenesis through p38δ inhibition. Consistent with the results obtained in animals, p38α was reduced in visceral and subcutaneous adipose tissue of subjects with obesity and was inversely correlated with body mass index (BMI).

Altogether, we have elucidated a mechanism implicated in physiological BAT activation that has potential clinical implications for the treatment of obesity and related diseases such as diabetes.


Cardioforo 2018: La ciencia básica al servicio de la salud cardiovascular (1 March 2018)

On Thursday 1 March 2018, Guadalupe Sabio will open the Cardioforo Interactivo 2018 in Badajoz (Spain) with the talk La ciencia básica al servicio de la salud cardiovascular.

Cardioforo Interactivo 2018

Proteínas del estrés en la lucha contra la obesidad

Our lab mate Leticia Herrera explains that the incidence of obesity has doubled since 1980, reaching more than 600 million obese adults in 2014 around the world.

[read more in CONEC]

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