2026-05-20T23:33:02Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65362024-09-27T08:20:33Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Quinones, Mar
author
Al-Massadi, Omar
author
Folgueira, Cintia
author
Bremser, Stephan
author
Gallego, Rosalia
author
Torres-Leal, Leonardo
author
Haddad-Tovolli, Roberta
author
Garcia-Caceres, Cristina
author
Hernandez-Bautista, Rene
author
Lam, Brian Y. H.
author
Beiroa, Daniel
author
Sanchez-Rebordelo, Estrella
author
Senra, Ana
author
Malagon, Jose A.
author
Valerio, Patricia
author
Fondevila, Marcos F.
author
Ferno, Johan
author
Malagon, Maria M.
author
Contreras, Raian
author
Pfluger, Paul
author
Bruening, Jens C.
author
Yeo, Giles
author
Tschoep, Matthias
author
Dieguez, Carlos
author
Lopez, Miguel
author
Claret, Marc
author
Kloppenburg, Peter
author
Sabio, Guadalupe
author
Nogueiras, Ruben
funder
Ministerio de Economía y Competitividad (España)
funder
Xunta de Galicia (España)
funder
Atresmedia
funder
Fundación AstraZeneca
funder
European Foundation for the Study of Diabetes
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
Western Norway Regional Health Authority (Noruega)
funder
Comunidad de Madrid (España)
funder
Fundación BBVA
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Unión Europea. Comisión Europea
funder
Fundação de Amparo à Pesquisa do Estado de São Paulo Minas Gerais (Brasil)
funder
Instituto de Salud Carlos III
2018-10-26T07:59:26Z
2018-10-26T07:59:26Z
2018
Nat Commun. 2018; 9(1):3432
10.1038/s41467-018-05711-6
2041-1723
Nature Communications
30143607
http://hdl.handle.net/20.500.12105/6536
p53 is a well-known tumor suppressor that has emerged as an important player in energy balance. However, its metabolic role in the hypothalamus remains unknown. Herein, we show that mice lacking p53 in agouti-related peptide (AgRP), but not proopiomelanocortin (POMC) or steroidogenic factor-1 (SF1) neurons, are more prone to develop diet-induced obesity and show reduced brown adipose tissue (BAT) thermogenic activity. AgRP-specific ablation of p53 resulted in increased hypothalamic c-Jun N-terminal kinase (JNK) activity before the mice developed obesity, and central inhibition of JNK reversed the obese phenotype of these mice. The overexpression of p53 in the ARC or specifically in AgRP neurons of obese mice decreased body weight and stimulated BAT thermogenesis, resulting in body weight loss. Finally, p53 in AgRP neurons regulates the ghrelin-induced food intake and body weight. Overall, our findings provide evidence that p53 in AgRP neurons is required for normal adaptations against diet-induced obesity.
eng
AGOUTI-RELATED PEPTIDE
ADIPOSE-TISSUE THERMOGENESIS
REGULATES FOOD-INTAKE
CONNECTS ER STRESS
ENERGY-BALANCE
ENDOPLASMIC-RETICULUM
HYPOTHALAMIC AMPK
GLUCOSE-HOMEOSTASIS
POMC NEURONS
METABOLIC-REGULATION
p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1
journal article
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p53InAgRPNeurons_2018.pdf
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p53InAgRPNeurons_2018_suppl.pdf
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p53InAgRPNeurons_2018.pdf.txt
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https://repisalud.isciii.es/bitstreams/c971efd4-4073-4029-b692-a2091ca3ae36/download
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p53InAgRPNeurons_2018_suppl.pdf.txt