2026-06-14T03:33:19Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/71612024-10-31T11:50:55Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Matesanz, Nuria
author
Nikolic, Ivana
author
Leiva, Magdalena
author
Pulgarin-Alfaro, Marta
author
Santamans, Ayelen M
author
Bernardo, Edgar
author
Mora, Alfonso
author
Herrera-Melle, Leticia
author
Rodriguez, Elena
author
Beiroa, Daniel
author
Caballero, Ainoa
author
Martin-Garcia, Elena
author
Acin-Perez, Rebeca
author
Hernández-Cosido, Lourdes
author
Leiva-Vega, Luis
author
Torres, Jorge L
author
Centeno, Francisco
author
Nebreda, Angel R
author
Enriquez, Jose Antonio
author
Nogueiras, Rubén
author
Marcos, Miguel
author
Sabio, Guadalupe
funder
European Foundation for the Study of Diabetes
funder
Fundación Lilly
funder
Unión Europea. Comisión Europea
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Junta de Castilla y León (España)
funder
Xunta de Galicia (España)
funder
Fundación ProCNIC
funder
Comunidad de Madrid (España)
funder
Government of Extremadura (España)
2019-02-11T11:52:16Z
2019-02-11T11:52:16Z
2018-07
PLoS Biol. 2018; 16(7):e2004455
10.1371/journal.pbio.2004455
1545-7885
1545-7885
PLoS biology
29979672
http://hdl.handle.net/20.500.12105/7161
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. 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 (p38δ Fab-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.
eng
p38α blocks brown adipose tissue thermogenesis through p38δ inhibition
journal article
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