2026-05-22T05:09:04Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/51182024-09-27T07:59:12Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Porteiro, Begona
author
Fondevila, Marcos F.
author
Delgado, Teresa C.
author
Iglesias, Cristina
author
Imbernon, Monica
author
Iruzubieta, Paula
author
Crespo, Javier
author
Zabala-Letona, Amaia
author
Ferno, Johan
author
Gonzalez-Teran, Barbara
author
Matesanz, Nuria
author
Hernandez-Cosido, Lourdes
author
Marcos, Miguel
author
Tovar, Sulay
author
Vidal, Anxo
author
Sanchez-Ceinos, Julia
author
Malagon, Maria M.
author
Pombo, Celia
author
Zalvide, Juan
author
Carracedo, Arkaitz
author
Buque, Xabier
author
Dieguez, Carlos
author
Sabio, Guadalupe
author
Lopez, Miguel
author
Aspichueta, Patricia
author
Martinez-Chantar, Maria L.
author
Nogueiras, Ruben
funder
Ministerio de Economía y Competitividad (España)
funder
Xunta de Galicia (España)
funder
Comunidad de Madrid (España)
funder
Fundación Sociedad Española se Endocrinología y Nutrición
funder
Instituto de Salud Carlos III
funder
Asociación Española Contra el Cáncer
funder
Basque Government (España)
funder
Fundación BBVA
funder
Fundación AstraZeneca
funder
Centro de Investigación Biomédica en Red - CIBEROBN (Fisiopatología de la Obesidad y Nutrición)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea
2017-10-20T10:23:12Z
2017-10-20T10:23:12Z
2017
Nat Commun. 2017; 8:15111
10.1038/ncomms15111
2041-1723
Nature Communications
28480888
http://hdl.handle.net/20.500.12105/5118
p53 family members control several metabolic and cellular functions. The p53 ortholog p63 modulates cellular adaptations to stress and has a major role in cell maintenance and proliferation. Here we show that p63 regulates hepatic lipid metabolism. Mice with liver-specific p53 deletion develop steatosis and show increased levels of p63. Down-regulation of p63 attenuates liver steatosis in p53 knockout mice and in diet-induced obese mice, whereas the activation of p63 induces lipid accumulation. Hepatic overexpression of N-terminal transactivation domain TAp63 induces liver steatosis through IKK beta activation and the induction of ER stress, the inhibition of which rescues the liver functions. Expression of TAp63, IKK beta and XBP1s is also increased in livers of obese patients with NAFLD. In cultured human hepatocytes, TAp63 inhibition protects against oleic acid-induced lipid accumulation, whereas TAp63 overexpression promotes lipid storage, an effect reversible by IKK beta silencing. Our findings indicate an unexpected role of the p63/IKK beta/ER stress pathway in lipid metabolism and liver disease.
eng
FATTY LIVER-DISEASE
ENDOPLASMIC-RETICULUM STRESS
UNFOLDED PROTEIN RESPONSE
B-KINASE-BETA
ER STRESS
KAPPA-B
LIPID-METABOLISM
MOUSE MODEL
IN-VIVO
P53
Hepatic p63 regulates steatosis via IKK beta/ER stress
journal article
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HepaticP63RegulatesSteatosis_2017.txt
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HepaticP63RegulatesSteatosis_2017_Supp.txt