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Title: Hepatic p63 regulates steatosis via IKKβ/ER stress.
Authors: Porteiro, Begoña
Fondevila, Marcos F
Delgado, Teresa C
Iglesias, Cristina
Imbernon, Monica
Iruzubieta, Paula
Crespo, Javier
Zabala-Letona, Amaia
Fernø, Johan
González-Terán, Bárbara
Matesanz, Nuria
Hernández-Cosido, Lourdes
Marcos, Miguel
Tovar, Sulay
Vidal, Anxo
Sánchez-Ceinos, Julia
Malagon, Maria M
Pombo, Celia
Zalvide, Juan
Carracedo, Arkaitz
Buque, Xabier
Dieguez, Carlos
Sabio, Guadalupe
López, Miguel
Aspichueta, Patricia
Martínez-Chantar, María L
Nogueiras, Ruben
metadata.dc.subject.mesh: Adult
Endoplasmic Reticulum Stress
Fatty Liver
I-kappa B Kinase
Lipid Metabolism
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Transcription Factors
Tumor Suppressor Proteins
X-Box Binding Protein 1
Issue Date: 8-May-2017
Abstract: 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 IKKβ activation and the induction of ER stress, the inhibition of which rescues the liver functions. Expression of TAp63, IKKβ 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 IKKβ silencing. Our findings indicate an unexpected role of the p63/IKKβ/ER stress pathway in lipid metabolism and liver disease.
metadata.dc.identifier.doi: 10.1038/ncomms15111
Appears in Collections:Producción 2020

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