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Tag: p38α (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.


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]

alimentación

CICERONE program 2017 for Masters and advanced undergraduate students

Though the CICERONE Program is open to Masters and advanced undergraduate students for extending their scientific training through hands-on experience of laboratory-based biomedical research during the summer recess. In addition to carrying out a supervised research project, the students also attend CNIC seminars.

The aim of the program is to give university students first-hand knowledge of biomedical research so that they can make more informed choices about the possibility of pursuing a scientific career.

Link Size
2017 Guidelines 386 KB
Application form
Document of acceptance 545 KB

For the 2017 call, we are offering two different research projects:

  • Role of p38MAPK in metabolic diseases: Metabolic syndrome is a medical disorder defined by the co-occurrence of obesity, impaired glucose tolerance, dyslipidemia and hypertension. Stress activated protein kinases have been shown to control both obesity by itself and diabetes associated to obesity. These stress kinases are activated by several MAPK activated kinases (MKK). We want to investigate the role of MKK3 in this process and the molecular mechanism by which this kinase could affect diabetes.
  • p38MAPK in heart phisiology: The p38 MAPK pathway transduces a variety of extracellular signals regulating cellular responses to stress, being implicated in cell proliferation, differentiation and apoptosis. Its implication in the development of human diseases it is being deeply studied. Four p38 MAPK family members have been identified: p38α, β, γ and δ.
    Preliminary data from our laboratory show that these kinases may control cytokine production during acute and chronic inflammatory processes. Moreover, studies with genetically modified mice made in our laboratory confirm that p38MAPKs have a role in the development of the heart. Our main objective is to determine if the regulation of the p38MAPK signaling pathway could have beneficial effects in the cardiac response to exercise.
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